Publication for SPINT1 and SPINT2

Species	Symbol	Function*	Entrez Gene ID*	Other ID	Gene coexpression	CoexViewer
hsa	SPINT1	serine peptidase inhibitor, Kunitz type 1	6692			[link]
hsa	SPINT2	serine peptidase inhibitor, Kunitz type 2	10653

Pubmed ID	Priority	Text
25786220	0.98	HAI-1 (middle panels), and HAI-2 (lower panels).
	0.98	HAI-2 acts in concert with HAI-1 to function as an inhibitor of matriptase in breast cancer cells.
	0.98	HAI-1 and HAI-2 result in the ability of HAI-1 but not HAI-2 to control matriptase activity in mammary epithelial cells.
	0.97	HAI-1 complex, three different matriptase-HAI-2 complexes, are formed following the induction of matriptase activation.
	0.97	SPINT1 and SPINT2 genes, which encode two highly related, integral membrane, Kunitz-type serine protease inhibitors, named hepatocyte growth factor (HGF) activator inhibitor type (HAI)-1 and 2.
	0.97	HAI-1 expression, and to a lesser extent with HAI-2, in human epithelial and carcinoma cells
	0.97	HAI-1 expression whereas two expressed HAI-2.
	0.97	HAI-2 is a more potent matriptase inhibitor than HAI-1.
	0.97	HAI-1 species using the HAI-1 mAb M19 or HAI-2 species using the HAI-2 mAb DC16.
	0.97	HAI-2 is a more potent inhibitor than HAI-1 (Fig. 2).
	0.96	HAI-1 complexes, but matriptase-HAI-2 complexes are not observed.
	0.96	HAI-1 species from the sample with the HAI-1 mAb (Fig. 2B, HAI-1, lane 4) or depleted the HAI-2 species with the HAI-2 mAb (Fig. 2B, HAI-2, lane 5).
	0.96	HAI-1:matriptase-HAI-2 ratio was determined to be around 1:2.5 by densitometry and analysis using ImageJ of the bands representing the 120-kDa (Fig. 2B, MTP, lane 5), and the 100-, and 130-kDa (Fig. 2B, total MTP, lane 4) matriptase complexes followed by normalization of these values by the value for the 70-kDa matriptase zymogen bands (Fig. 2B, MTP, lanes 4 and 5).
	0.96	HAI-1, but not HAI-2, is the predominant inhibitor of matriptase in human mammary epithelial cells.
	0.96	HAI-1 remained after the removal of the HAI-2 species by immunodepletion using HAI-2 mAb DC16-Sepharose (Fig. 3C, lane 3).
	0.96	HAI-2 should be able to inhibit matriptase in a very similar manner to HAI-1.
	0.95	HAI-1 expression is 1 (rho< 0.0001) and between matriptase and HAI-2 is 0.74015 (rho< 0.0001).
	0.95	HAI-1 complex and the 130-kDa matriptase-HAI-2 complex appear as one large merged band in the immunoblot analysis using the matriptase mAb (Fig. 2B, Total MTP, lane 3).
	0.95	HAI-2, the majority being bound to active matriptase to form the two complexes (Fig. 2B, HAI-2 lane 3), whereas only 18% of the available HAI-1 was bound to matriptase in the 120-kDa complex (Fig. 2B, HAI-1, lane 3).
	0.95	HAI-1 depleted mixture, and the HAI-2 depleted mixture were analyzed for matriptase species, HAI-1 species, and HAI-2 species by immunoblot using the matriptase mAb M24 (Total MTP), the HAI-1 mAb M19 (HAI-1) and the HAI-2 mAb DC16 (HAI-2), respectively.
	0.95	HAI-2, like HAI-1, undergo synthesis and post-translational modification through the secretory pathway and become anchored in the cell membrane.
	0.94	HAI-2 is also a potent matriptase inhibitor in solution, but in spite of this, HAI-2 inhibition of matriptase is not observed in all contexts where HAI-2 is expressed, unlike what is seen for HAI-1.
	0.94	HAI-2 complexes of 100-, 120-, and 130-kDa along with the formation of the 120-kDa matriptase-HAI-1 complex (Fig. 3B, comparing lanes 2 with lanes 1).
	0.94	HAI-1 and HAI-2 complexes contain matriptase.
	0.93	HAI-1 complex versus matriptase-HAI-2 complexes compared to the ratio of the uncomplexed HAI-1 versus HAI-2.
	0.93	HAI-1 mAb M19 (lane 2) or the HAI-2 mAb DC 16 (lane 3).
	0.92	HAI-2 (Fig. 1) and the greater potency for matriptase inhibition than cellular HAI-1 (Fig. 2), one might expect that HAI-2 is an important endogenous matriptase inhibitor.
	0.91	HAI-1 probably has better access to active matriptase than HAI-2, which is supported by the higher levels of matriptase-HAI-1 complex than matriptase-HAI-2 complexes detected by immunoblot analysis (Fig. 3).
	0.90	HAI-1 is about 2.2 (1/2.5/0.18 = 2.2) times greater than HAI-2 prior to the incubation with active matriptase, which is in marked contrast to the matriptase-HAI-1:matriptase-HAI-2 ratio (1:2.5) after incubation with active matriptase.
	0.87	HAI-1 mAb M19 or the HAI-2 mAb DC 16.
	0.85	HAI-1 and HAI-2 to inhibit active matriptase.
	0.80	HAI-2 with matriptase (A-C), activated matriptase (D-F), and HAI-1 (G-I) in T-47D human breast cancer cells was analyzed by immunofluorescent double staining with (D-I) and without (A-C) permeabilization of the cells.
	0.77	HAI-1, but not HAI-2, is the predominant endogenous inhibitor of matriptase activity.
	0.74	HAI-2 and HAI-1 takes place on the cell surface.
	0.71	HAI-2 immunodepletion was the 70-kDa matriptase zymogen, free HAI-1 and the 120-kDa matriptase-HAI-1 complex (Fig. 2B, lanes 5 under total MTP and HAI-1,) which again verifies the specificity of immunodepletion.
	0.63	HAI-1 and HAI-2 work in concert to inhibit matriptase.
	0.60	HAI-1 and HAI-2 are capable forming stable complexes with active matriptase in solution and that cellular HAI-2 appears to be a more effective matriptase inhibitor than cellular HAI-1.
	0.53	HAI-2 complexes are generally of low abundance and so the 130-kDa species is easily masked by the much more abundant 120-kDa matriptase-HAI-1 complex.
23333561	0.98	HAI-1, HAI-2, or HAI-2-EYFP.
	0.98	HAI-2 or HAI-1.
	0.97	HAI-2, HAI-2-EYFP or HAI-1 : It has previously been reported that matriptase levels are low in the cells when exogenously expressed alone, a phenomenon that can be counteracted by co-expression of HAI-1.
	0.97	HAI-2 or HAI-2-EYFP resulted in almost identical matriptase protein levels as that observed for the matriptase and HAI-1 co-expression (Fig. 2 B and C, lanes 4-6).
	0.97	HAI-1 or HAI-2 contained 105 fold more matriptase mRNA/18S (data not shown).
	0.97	HAI-2 and HAI-2-EYFP function in a manner similar to HAI-1, resulting in a higher level of matriptase in the cells.
	0.97	HAI-2 has a similar effect, MDCK cells were transiently transfected with a matriptase vector alone or in combination with a vector coding for either HAI-1, HAI-2 or HAI-2-EYFP.
	0.97	HAI-1, or matriptaseS805A and HAI-2 along with Mock-transfected cells in order to determine the background level of peptidolytic hydrolysis.
	0.97	HAI-1, or matriptaseS805A and HAI-2 all showed a rate of substrate conversion in the order of 0.2-0.4 mAU/min similar to the Mock extracts (Fig. 4).
	0.97	HAI-2 is responsible for this activity of HAI-2 and that HAI-1 has the same ability.
	0.97	HAI-1 or HAI-2 in the presence of 1 muM of the matriptase inhibitor aprotinin.
	0.96	HAI-2 is smaller and less complex than HAI-1 and may therefore shed light on the function of HAIs during expression of matriptase.
	0.96	HAI-1 or HAI-2 immunoreactivity could be detected in any of the immunoprecipitates (data not shown).
	0.96	HAI-1 or HAI-2 as compared to the basal level observed for HAI-1 or HAI-2 expressed alone (Fig. 4).
	0.96	HAI-1, HAI-2 or HAI-2-EYFP were compared to non-transfected (MDCK) and lambda-DNA (Mock) transfected cells by SDS-PAGE and western blotting.
	0.95	HAI-1 or HAI-2 (Fig. 2B and C, lane 3).
	0.95	HAI-1 or HAI-2 causes matriptase to accumulate on the plasma membrane co-localizing with the surface marker phalloidin.
	0.95	HAI-1 and HAI-2 are able to inhibit proteolytic release of matriptase.
	0.95	HAI-1 or HAI-2-EYFP, and grown for 48 h on transwell filters before fixation and immunocytochemical staining with M32 (targeting total matriptase) and the cell surface-marker phalloidin (targeting F-actin).
	0.94	HAI-2 and HAI-1 are type I transmembrane serine protease inhibitors belonging to the Kunitz family with a short intracellular tail and a larger extracellular part containing two inhibitory Kunitz domains (KD).
	0.94	HAI-1 or HAI-2 seems to stem from a serine protease as the activity is blocked by the presence of a range of serine proteases inhibitors including aprotinin.
	0.93	HAI-1 or HAI-2 accumulates on the plasma membrane where it is activated, as judged by cleavage at Arg614 and increased peptidolytic activity of the cell extracts.
	0.93	HAI-1 and HAI-2 are thus via their Kunitz domain 1, able to reduce release of the ectodomain of matriptase.
	0.92	HAI-1 and HAI-2, respectively, co-transfected with Mock (light gray columns), native matriptase (Mat, medium gray columns) and as a control matriptase S805A (S805A, dark gray columns).
	0.91	HAI-1 or HAI-2, we decided to test the enzymatic activity of cell extracts and media towards a peptide based chromogenic substrate, isoleucil-prolyl-arginine-p-nitroaniline.
	0.90	HAI-1 or HAI-2 down to the Mock background (Fig. 4, the three outmost columns to the right).
	0.88	HAI-2 alone, as hepatocyte growth factor activator inhibitor-1 (HAI-1) encoded by the SPINT1 gene, also acts as an inhibitor of matriptase.
	0.88	HAI-2 or HAI-1 is rapidly transported through the secretory pathway and shed, whereas matriptase expressed together with HAI-2 accumulate on the plasma membrane as a result of a process dependent on Kunitz domain 1 of HAI-2.
	0.88	HAI-1, HAI-2 or HAI-2-EYFP omitted very few cells appeared to contain matriptase, which is in agreement with our previous findings (Fig. 2B, lane 3).
	0.85	HAI-1, HAI-2, and HAI-2-EYFP were collected and immunoprecipitated using the antibodies against matriptase coupled to sepharose.
	0.83	HAI-1 and HAI-2 important for development of the placenta.
	0.79	HAI-2 or HAI-1 since matriptase mRNA levels are similar.
	0.79	HAI-2, HAI-2 R48L, HAI-2 R143L, and HAI-2 R48L/R143L or HAI-1 were analyzed on western blots using antibodies against HAI-2 (E) or matriptase (F).
30777474	0.98	HAI-1 and HAI-2 were arranged in the order of the amount of matriptase expression.
	0.97	HAI-2 in matriptase regulation in neoplastic B-cells, the global expression status of matriptase in relation to HAI-1 and HAI-2 at the mRNA level in haematological cancer cells versus epithelial/carcinoma cells was analysed in the 945 human cancer cell lines collected in the Cancer Cell Line Encyclopaedia (CCLE) database.
	0.97	HAI-1 and HAI-2 together was seen only in approximate one-fifth of these matriptase-expressing haematological cancer lines (10 out of 51; 20%) (Figure 1(B)).
	0.97	HAI-2 appears to be expressed at lower levels in matriptase-positive haematological cells compared to epithelial cells, the effect is not as marked as it is for HAI-1 (Figure 2(A)).
	0.97	HAI-2 in the absence of HAI-1 (Figure 2(B)).
	0.97	HAI-1 and HAI-2 together, or HAI-2 alone, or HAI-1 alone.
	0.96	HAI-2, another membrane-associated Kunitz-type serine protease inhibitor, highly related to HAI-1, has also been shown to be able to inhibit matriptase activity and to support matriptase synthesis and intracellular trafficking.
	0.96	HAI-1 alone, HAI-2 alone, or lack of HAIs co-expression was presented in the Pie chart of the epithelial origin or haematological origin, respectively.
	0.96	HAI-2 than HAI-1.
	0.96	HAI-2/matriptase mRNA compared to log HAI-1/matriptase mRNA suggests that haematological cancer cells have a tendency to express higher levels of HAI-2 than HAI-1.
	0.96	HAI-1 and HAI-2.
	0.95	HAI-1 (spint1), and HAI-2 (spint2) in the whole cancer cell lines from CCLE were comprehensively retrieved, presented, and compared using the UCSC Xena Platform.
	0.91	HAI-2 appears to be co-expressed with matriptase at higher frequency than HAI-1 in haematological cancer lines.
	0.86	HAI-1:matriptase mRNA ratio and the HAI-2:matriptase mRNA ratio were calculated for these matriptase-expressing cells and are presented on a logarithmic scale sorted by their cellular origins in a scatter plot (Figure 2(C)).
	0.85	HAI-1 indicates that other related inhibitor, such as HAI-2, might be expressed.
	0.83	HAI-2 more frequently than HAI-1 in human neoplastic B-cells in contrast to epithelial/carcinoma cells where matriptase is typically co-expressed with both HAI-1and HAI-2
	0.83	HAI-1 and HAI-2 together (Figure 1(B)), consistent with our previous study in which all 21 matriptase-expressing epithelial/carcinoma lines express both HAI-1 and HAI-2 at protein levels.
	0.81	HAI-2 and HAI-1 are expressed at high levels in 184 A1N4 human mammary epithelial cells and HaCaT human keratinocytes, HAI-1, and not HAI-2, represents the predominant protease inhibitor for the control of matriptase proteolytic activity.
	0.78	HAI-1:matriptase or HAI-2:matriptase expression was calculated from the epithelial origin and haematological origin retrieved from CCLE database, respectively.
	0.75	HAI-2 as it is for HAI-1.
	0.68	HAI-1 and HAI-2 at protein levels in seven matriptase-expressing neoplastic B-cells.
	0.64	HAI-1, and HAI-2 mRNA expression levels (Log RPKM) of eight major blood cancer subclasses were retrieved from the histological type of "haematopoietic and lymphoid tissue classification" in the CCLE database.
	0.64	HAI-1 and HAI-2 were almost ubiquitously co-expressed at high levels.
	0.62	HAI-2 (B and C), and HAI-1 (D).
27043831	0.98	HAI-2, a Kunitz inhibitor that is highly related to HAI-1, has been shown to also be a matriptase inhibitor in breast cancer cells, but not in cultured mammary epithelial cells.
	0.97	HAI-1 and HAI-2 are expressed at high levels by mammary epithelial cells, we hypothesize that the target proteases of both Kunitz inhibitors might be actively involved in lactation, and if so, having subsequently been inactivated by forming complexes with HAI-1 and HAI-2 and secreted they should be detectable in the milk.
	0.97	HAI-1, HAI-2, and matriptase (MTP), as indicated.
	0.97	HAI-2 containing fractions eluted from the CM-Sepharose were subjected to immunoaffinity chromatography on a HAI-1 mAb M19-Sepharose column followed by a HAI-2 mAb DC16-Sepharos column.
	0.97	HAI-1 and HAI-2 species, we developed a purification scheme that combined conventional liquid chromatography and immunoaffinity chromatography and that is summarized in Fig 1B.
	0.97	HAI-1 complex and the vast majority of the HAI-2 complexes, was further fractionated by DEAE chromatography.
	0.97	HAI-1 and prostasin HAI-2 complexes were needed for the Western blot analysis.
	0.96	HAI-1 and HAI-2.
	0.96	HAI-2 complex were applied to the HAI-1 mAb M19-Sepharose column to deplete the sample of the previously well-characterized 95-kDa matriptase-HAI-1 complex.
	0.96	HAI-1 mAb M19-Sepharose (A.) or HAI-2 mAb DC16-Sepharose (B.) immunoaffinity columns were analyzed by immunoblot using the three prostasin mAbs, YL11, YL10, and YL89 under non-boiled, non-reducing conditions (lanes 1) or boiled, non-reducing conditions (lanes 2).
	0.96	HAI-1 and HAI-2 species expressed by human mammary epithelial cells.
	0.95	HAI-1, HAI-2, and their complexes were examined in the human mammary epithelial line MTSV 1.7, which was originally isolated and immortalized from human breast milk.
	0.95	HAI-1 and HAI-2 complexes detected in milk.
	0.95	HAI-2 can replace and/or function in concert with HAI-1 in the control of matriptase in monocytes/macrophages.
	0.93	HAI-1 and HAI-2.
	0.92	HAI-1 and HAI-2 in human milk suggests that the membrane-associated serine proteases matriptase and prostasin are significantly active but under tight control during lactation.
	0.90	HAI-1 and HAI-2 complexes in human milk.
	0.89	HAI-1 and HAI-2 complexes with matriptase and prostasin given that these protease-inhibitor complexes with the exception of prostasin-HAI-2 complex were detected in milk-derived mammary epithelial cells.
	0.89	HAI-1 complexes, human milk contains matriptase-HAI-2, protsatin-HAI-1 and prostasin-HAI-2 complexes.
	0.84	HAI-1 and HAI-2 in Human Milk: Significant Proteolysis in Lactation
	0.69	HAI-1 and HAI-2 in human milk suggests that matriptase and prostasin are the physiologically relevant target proteases of HAI-1 and HAI-2 in this system.
	0.64	HAI-1 and HAI-2 which is closely related to HAI-1.
26171609	0.98	HAI-1-depleted conditioned medium (lanes 2), and matriptase-depleted medium (lanes 3) were analyzed by immunoblot for HAI-2 species with N-glycan branching using the mAb DC16 (HAI-2 DC16), HAI-2 species without N-glycan branching using the mAb XY9 (HAI-2 XY9), total matriptase using the mAb M24 (Total MTP), activated matriptase using the mAb M69 (Act-d MTP), and HAI-1 using the mAb M19 (HAI-1).
	0.97	HAI-2 species also contained matriptase and to determine the extent to which HAI-2 contributes to matriptase inhibition relative to HAI-1, we conducted immunodepletion experiments with a HAI-1 mAb (Fig 5, lanes 2) and a matriptase mAb (Fig 5, lanes 3) using the conditioned medium (Fig 5B, lanes 1).
	0.96	HAI-1 and the HAI-2 species with N-glycan branching.
	0.96	HAI-2 complex relative to the 110- and 95-kDa matriptase-HAI-1 complexes appeared to be quite low (Fig 5 Act-d.
	0.95	HAI-2/PB reflect the functionality and protein domain structure of this Kunitz inhibitor which is related to HAI-1 and bikunin.
	0.95	HAI-1 and HAI-2 are not only unique among the 18 human Kunitz-containing proteins (Fig 7) but also confer on HAI-1 and HAI-2 their inhibitory potency and specificity to HGF activator, matriptase and prostasin observed in solution.
	0.93	HAI-1 possesses an LDL receptor class A domain and a MANEC domain, neither of which are present in HAI-2.
	0.82	HAI-1, HAI-2, and bikunin (Alpha-1-microglobulin/bikunin precursor, AMBP) are compared.
	0.68	HAI-1 and to minor extent by HAI-2 with N-glycan branched glycosylation.
	0.55	HAI-2/PB might be more closely related to bikunin than HAI-1.
	0.50	HAI-1 versus HAI-2.
25268161	0.98	HAI-1 and HAI-2 inhibit, not only HGFA, but also other HGF/SF-activating proteases, such as matriptase and hepsin.
	0.98	HAI-1 and HAI-2, have crucial roles in the regulation of these HGF/SF-activating proteases in tumor tissues.
	0.97	HAI-1 is expressed by most epithelial cells, whereas HAI-2 is ubiquitously expressed in normal tissues.
	0.97	HAI-1, HAI-2 downregulation and its correlation with disease progression have been observed in many cancers, including malignant brain tumors, renal cell carcinoma, hepatocellular carcinoma, gastric adenocarcinoma, esophageal squamous cell carcinoma, ovarian carcinoma, prostate adenocarcinoma, and breast carcinoma.
	0.95	HAI-1 and HAI-2, in carcinogenesis and cancer cell biology.
	0.89	HAI-1 and HAI-2 were initially purified from conditioned medium of the MKN45 human gastric carcinoma cell line as an efficient inhibitor of HGFA.
	0.87	HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment.
	0.59	HAI-1, while for HAI-2 two major splicing variants (HAI-2-long and HAI-2-short) have been reported.
27167193	0.98	SPINT1 and to SPINT2 by cancer stages (I-II, III-IV, and unclassified), by ER expression status (ER+, ER-, and unclassified), and by breast cancer subtypes (Luminal A, Luminal B, TN, HER2+, and unclassified).
	0.96	SPINT1, gray box, ST14/Prss14 to SPINT2, white box, average of ST14/Prss14 to SPINT1, M1, average of ST14/Prss14 to SPINT2, M2.
	0.93	SPINT1, SPINT2 and ratios of ST14/Prss14 to SPINT1 and SPINT2
	0.92	SPINT1 and SPINT2, seem to add another level of complexity.
	0.89	SPINT1, gray box, SPINT2, white box.
	0.85	SPINT1 and SPINT2 expression levels are not different in the cancer stages I-II and III-IV (Figure 2A), SPINT2 expression levels were somewhat lower in ER- and TN breast cancer groups (Mean differences of SPINT2, ER- vs. ER+, P < 0.01, TN vs. luminal A, P < 0.01, TN vs. luminal B, P < 0.01, TN vs. HER2.
	0.85	SPINT1 (I) and to SPINT2 (II) in stages III-IV group, and ER- group.
	0.85	SPINT1 and SPINT2 (Figure 6A and 6B).
25910030	0.98	SPINT1 and SPINT2 that were observed in aggressive cancer cells may lead to the higher levels of available proteolytic HGF activators (HGFA, matriptase, and hepsin) resulting in promotion of tumor growth and invasion.
	0.97	SPINT1 and SPINT2 respectively).
30765871	0.98	HAI-1 and HAI-2 in a cell invasion progression model of lung cancer (CL1-0 and CL1-5).
	0.71	Hepatocyte growth factor activator inhibitor-2 (HAI-2) is a bi-Kunitz-type serine protease inhibitor containing two Kunitz domains (KD1 and KD2), first identified in placenta and gastric carcinoma cells with a homology to HAI-1, and has an inhibitory activity against hepatocyte growth factor activator (HGFA).
29438412	0.97	HAI-1 and HAI-2 in human foreskin.
	0.97	HAI-2 and HAI-1 in the inhibition of prostasin and matriptase are correlated with their different tissue distribution and subcellular localization
	0.97	HAI-1 is primarily targeted to the intercellular contacts and HAI-2 largely remains inside HaCaT human keratinocytes.
	0.97	HAI-2 (A and B) and HAI-1 (C and D) in HaCaT human keratinocytes were analyzed by indirect immunofluorescent staining with the HAI-2-specific mAb DC16 and HAI-1-specific mAb M19, followed by Alexa 594-labelled anti-mouse IgG. The cells were also stained for F-actin using Alexa 488-labelled phalloidin (B and D, green) and nuclei using DAPI (B and D, blue), as counterstain.
	0.96	HAI-1 and not HAI-2 is the main inhibitor of both prostasin and matriptase.
	0.93	HAI-1 and HAI-2 can also be observed in vitro using HaCaT human keratinocytes (Fig 7).
	0.92	HAI-1, and HAI-2 in human skin
	0.92	HAI-1 but not HAI-2 is the prominent inhibitor for prostasin and matriptase in skin.
	0.91	HAI-2, HAI-1 was detected on the surface of the keratinocytes in all three viable epidermal layers (Fig 6C).
	0.89	HAI-2 and HAI-1 is consistent with their synthesis and maturation through the secretory pathway.
	0.85	HAI-1 and HAI-2 was analyzed and compared in human skin specimens by immunohistochemistry and immunoblot assays.
	0.83	HAI-2 versus HAI-1.
	0.64	HAI-2 mAb DC16 (A and B), the HAI-1 mAb M19 (C and D), and mouse IgG as negative control (data not shown).
	0.63	HAI-1 or HAI-2.
	0.58	HAI-1 and HAI-2 in human skin.
24121274	0.97	HAI-2 expression but not that of HAI-1 was down-regulated approximately by 50% in N2 cells following progression whereas the matriptase expression level was significantly increased in N1 and N2 cells (Figure 1C).
	0.97	HAI-2 protein levels, but not those of HAI-1, fell progressively, whereas in contrast, the matriptase protein level increased (Figure 1D, left three columns).
	0.97	HAI-1, HAI-2 and matriptase expression using qPCR as well as the protein levels of matriptase and HAI-2 in the tumor tissues showed that matriptase knockdown or HAI-2 overexpression did not significantly affect the expression of the other two genes, and this silencing or overexpression in N2 cells remained stable during the in vivo experiments (Supplementary Figures 3A & 3B).
	0.96	HAI-1 did not significantly change during the orthotopic growth of PCa cells and in HAI-2-overexpressing and matriptase-silencing N2 xenograft tumors (Supplemental Figure 3).
	0.95	HAI-2 but not HAI-1 was significantly decreased throughout the progression and occurred in parallel with increased activation of matriptase.
	0.92	HAI-1 and HAI-2 primers and using GAPDH as an internal control.
	0.89	HAI-1 and HAI-2, and/or increased matriptase have been implicated in PCa progression.
	0.86	HAI-2 was isolated from the conditioned medium of a human stomach carcinoma cell line, identified as a serine protease inhibitor, and named after its homolog HAI-1.
	0.82	HAI-1, HAI-2 and matriptase by qPCR in the cells of this cancer progression model.
	0.67	HAI-1 and HAI-2 mRNA levels by q-PCR in 103E, N1 and N2 cells.
	0.65	HAI-2 to decrease complex formation between matriptase and HAI-1 might be that high levels of HAI-2 may complete with HAI-1 as an inhibitor for the formation of complexes with activated matriptase, resulting in the loss of matriptase/HAI-1 complexes, since both HAI-1 and HAI-2 have similar in vitro properties as catalytic inhibitors of matriptase.
	0.54	HAI-2 overexpression in PCa cells reduced the levels of matriptase/HAI-1 complexes, a surrogate to indicate the activated level of matriptase.
28125689	0.97	HAI-1 complex but did not remove the HAI-2 complexes (Fig 1, lanes 3).
	0.97	HAI-1 and HAI-2.
	0.97	HAI-1 may be a relatively standard event in the cells that express both proteins, the role of HAI-2 in prostasin inhibition may be rather more cell-line, or cell-type selective.
	0.94	HAI-1 or HAI-2.
	0.94	HAI-1 and HAI-2, and that it most likely acts on substrates inside the cells.
	0.92	HAI-1 and HAI-2 and matriptase by HAI-1 in human enterocytes.
	0.83	HAI-1 is a universal prostasin inhibitor whereas prostasin inhibition by HAI-2 appears to be cell-type selective
	0.79	HAI-2 or HAI-1 in human enterocytes in vivo.
	0.79	HAI-1 and HAI-2 are potent inhibitors of matriptase and prostasin.
18691255	0.97	HAI-1 and HAI-2.
	0.67	HAI-1 and HAI-2, should be addressed in further studies.
30388869	0.97	HAI-1/SPINT1 can complex with activated HGFAC on the surface of epithelial cells that are expressing both HAIs, suggesting that HAI-2/SPINT2 does not function as an HGFAC inhibitor on the cell surface.
	0.90	HAI-2/SPINT2 is another type 1 transmembrane Kunitz-type inhibitor with Kunitz domains homologous to those of HAI-1/SPINT1.
30755669	0.97	Hepatocyte growth factor activator inhibitor 1 (HAI-1) likewise inhibits KLK5, and the related Kunitz-type inhibitor HAI-2, formerly known as "placental bikunin", also strongly inhibits kallikrein-related peptidases, although its activity against KLK5 specifically has not been reported.
	0.95	HAI-2 (and perhaps HAI-1); in addition to inhibiting KLK5 as described above, these inhibitors are potent regulators of HGFA, hepsin, and matriptase, all serine proteases that activate pro-HGF/SF to active HGF/SF.
29890660	0.97	HAI-1, HAI-2, and matriptase mRNA in RCC cell lines using real-time quantitative PCR (RT-qPCR).
30623107	0.97	HAI-1 and HAI-2, HAI-2 could not compensate for loss of HAI-1 and vice versa, and silencing of SPINT1 or SPINT2 produces specific and differing phenotypes, suggesting that these two protease inhibitors have distinct roles in epithelial cells.
27870503	0.96	HAI-1 and HAI-2 have been shown to inhibit hepsin activity in cell-free enzyme inhibition assays.
	0.93	HAI-1 and HAI-2 are cell-surface endogenous inhibitors of both matriptase and hepsin
	0.83	HAI-1 and HAI-2.
12793903	0.96	HAI-1 and HAI-2, in addition to Met, might provide useful information.
	0.94	HAI-1 and HAI-2.
18506145	0.96	Spint1 and Spint2 are Kunitz-type serine protease inhibitors that regulate hepatocyte growth factor (HGF) activity through inhibition of HGF activator (HGFA), matriptase and hepsin (Parr and Jiang, 2006).
	0.96	Spint1 and Spint2 serve to inhibit the activity of HGF, these genes have been characterised as tumour suppressors (Morris et al, 2005).
24204759	0.96	hepatocyte growth factor activator inhibitor (HAI)-1 [reviewed in ] or HAI-2.
31737572	0.96	SPINT1, SPINT2, TFPI2 (tissue factor pathway Inhibitor 2), and WFDC2 (HE4).
29545930	0.95	HAI-2 reversion cell line (SAS/HAI-2rev) by the transfection of the HAI-2 expression vector into SAS/HAI-2KO#1 (Figure 1D).
	0.90	SPINT2-/- sublines were successfully established from each HaCaT and SAS line (HaCaT/HAI-2KO#1, HaCaT/HAI-2KO#2, SAS/HAI-2KO#1 and SAS/HAI-2KO#2) and one SPINT2-/- subline from HSC3 (HSC3/HAI-2KO) (Figure 1B).
	0.90	SPINT2-/- sublines (HAI-2KO#1 and #2) and one SPINT1-/- sublines (HAI-1KO) in each of HaCaT or SAS cell line, as well as one SPINT2-/- subline (HAI-2KO) in HSC3.
	0.90	SPINT2, knockout of SPINT1 resulted in enhanced Matrigel invasion capacity of SAS cells, confirming the previously reported anti-invasive role of HAI-1 in OSCC (Figure 3C).
	0.90	HAI-2 reversion (HAI-2rev) in SAS/HAI-2KO#1 cells on the prostasin protein level.
	0.90	SPINT2-/- SAS (SAS/HAI-2KO#1) (A) and SPINT2-/- HSC3 cells (B) under normoxic condition.
	0.89	Hepatocyte growth factor activator inhibitor (HAI)-1/SPINT1 and HAI-2/SPINT2 are membrane-anchored protease inhibitors having homologous Kunitz-type inhibitor domains.
	0.89	HAI-1 enhanced cellular invasion but suppressed proliferation, loss of HAI-2 suppressed both invasion and proliferation.
	0.88	HAI-1 suppresses the neoplastic progression of keratinocytes to invasive squamous cell carcinoma (SCC) through matriptase inhibition, the role of HAI-2 in keratinocytes is poorly understood.
	0.76	HAI-2, HaCaT cells also showed suppressed growth in the absence of HAI-1 (Figure 2A and Supplementary Figure 3).
	0.75	HAI-2 on the invasive capacity of OSCC cells are quite different from those of HAI-1.
	0.74	HAI-1, whereas they are strongly positive for HAI-2.
	0.71	HAI-2 (mAb 2A6121) and HAI-1 (mAb M19) were performed using cellular extracts.
	0.66	HAI-2, it was inhibited by HAI-1.
	0.61	HAI-1 depletion enhanced invasiveness as reported previously, indicating the role of HAI-2 is distinct from that of HAI-1 in neoplastic keratinocytes.
24940735	0.95	SPINT1/Hai1 (r = 0.88) and SPINT2/Hai2 (r = 0.66).
27936035	0.94	HAI-2 complex (band b), and matriptase-HAI-1 complex (band c).
	0.93	hepatocyte growth factor activator inhibitor (HAI)-1 and HAI-2.
	0.90	HAI-2 in the hematological cancer cell lines (Fig 3A, lanes 2, band b) or with HAI-1 in the three carcinoma cell lines (Fig 3B, lanes 2, band c).
	0.89	HAI-1 complex in the data presented, the control cells appear to exhibit higher levels of matriptase zymogen activation than the HAI-2-reduced cells.
	0.86	HAI-1 or HAI-2 (Fig 5A).
	0.66	HAI-1 complexes are higher in the HAI-2-reduced cells than the control cells.
26435753	0.94	SPINT1 and SPINT2, that encode serine peptidase inhibitors Kunitz type 1 and type 2, respectively, two potent inhibitors of HGF activator and of matriptase.
	0.91	SPINT1 and SPINT2 (encode serine peptidase inhibitors Kunitz type 1 and type 2, respectively, two inhibitors of HGF activator and of matriptase).
	0.70	SPINT1 (d), and SPINT2 (e) in insulinomas graded according to 2014 ENETS/WHO classification (G1, G2 and hepatic metastases).
	0.60	SPINT1 mRNA (Panel D) was lower in the three metastases in comparison to G1 insulinomas (P = 0.0250), whereas no difference was detected in SPINT2 gene expression (Panel E).
16636206	0.94	HAI-1 and HAI-2, also known as bikunin; Table I).
28287265	0.94	SPINT1, SPINT2, GLG1, ADAM10, and TACSTD2, which are expressed at lower levels in claudin-low cell lines and the 18 CLDN3-low CPTAC tumors.
32219002	0.94	HAI-1 have been observed in patients with benign lesions compared with those with prostate cancer, and the level of HAI-2 was decreased in highly invasive and progressed prostate cancer cells.
30601807	0.92	HAI-1 or HAI-2.
	0.91	HAI-1 co-expression showed no LC rescue, we observed rescuing activity of human prostasin after co-expression with HAI-2 in tpr mutants, i.e. the embryos show normal tracheal LC (Fig 6L).
	0.82	HAI-1 (H), or btl-Gal4/UAS-matriptase,UAS-HAI-2 (I), stained with CBP (A-E), or anti-Spectrin (magenta) and anti-GFP (green) antibodies (F), or anti-Spectrin (magenta) and anti-matriptase (green) antibodies (G-I).
29617460	0.91	HAI-1 (H1), HAI-2 (H2), and protein nexin-1 (PN-1) and wildtype (A), catalytically-inactive S238A (B), and zymogen-locked R44Q (C) variants of prostasin after pre-incubation with (A-C, lanes 2, 4, 6, and 8) or without (A-C, lanes 1, 3, 5, and 7) recombinant human matriptase.
20628393	0.89	HGF activator-1 (HAI-1), an HAI-2 homologue, may activate an EMT programme in these cells by up-regulating the transcription factor SIP-1/ZEB-2 and consequently repressing E-cadherin.
24498351	0.85	HAI-1, HAI-2, and serpinA1/alpha1-antitrypsin.
1306071	0.84	HAI 1, left) and severe sinusoidal lymphocytic reaction (HAI 2, right).
26715240	0.81	HAI-1 and HAI-2, or the irreversible serine protease inhibitor, protease nexin-1 (PN-1),.
27316827	0.75	HAI-1 and HAI-2.
27819674	0.70	HAI-1 and HAI-2) are potent matriptase inhibitors reducing invasion and metastasis in TNBC.
29987920	0.69	HAI-1/SPINT1 (SPINT1) and HAI-2/SPINT2 (SPINT2) are also shown.
	0.51	HAI-1, and HAI-2 in the cultured U87 glioblastoma cell line and its mock-transfected (mock) and SPINT2 expression vector-transfected (SPINT2) sublines.
30087389	0.66	HAI-1 and HAI-2, encoded by the genes serine peptidase inhibitor Kunitz type -1 and -2 (SPINT1 and SPINT2).
	0.55	HAI-1 and HAI-2 has clearly helped to understand how the enzymatic activity and the oncogenic potential of matriptase is tightly regulated and controlled.
24978308	0.66	HAI-1 and HAI-2 contain two kunitz-type inhibitor domains that have been found to be potent inhibitors of a number of trypsin-like, serine proteases, including hepatocyte growth factor activator.