High Hepsin expression predicts poor prognosis in Gastric Cancer

Zhang, Mingming; Zhao, Junjie; Tang, Wenyi; Wang, Yanru; Peng, Peike; Li, Lili; Song, Shushu; Wu, Hao; Li, Can; Yang, Caiting; Wang, Xuefei; Zhang, Chunyi; Gu, Jianxin

doi:10.1038/srep36902

Cited by 15 publications

(15 citation statements)

References 41 publications

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“…Hepsin is another efficient cellular activator of HGF/SF . It is expressed in the liver, kidney and some other epithelial tissues (Table ) and is reported to be involved in the progression of prostatic, renal, gastric, ovarian, and breast cancers . Meanwhile, matriptase and hepsin cleave the extracellular domains of various RTKs, such as epidermal growth factor receptor (EGFR), Her2, insulin receptor, insulin‐like growth factor‐1 receptor, and PDGFR .…”

Section: Ttsps: Localized Cellular Activators Of Hgf/sf In Epithelialmentioning

confidence: 99%

Hepatocyte growth factor activator inhibitors (HAI‐1 and HAI‐2): Emerging key players in epithelial integrity and cancer

Kataoka

Kawaguchi

Fukushima

et al. 2018

Pathology International

129

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The growth, survival, and metabolic activities of multicellular organisms at the cellular level are regulated by intracellular signaling, systemic homeostasis and the pericellular microenvironment. Pericellular proteolysis has a crucial role in processing bioactive molecules in the microenvironment and thereby has profound effects on cellular functions. Hepatocyte growth factor activator inhibitor type 1 (HAI-1) and HAI-2 are type I transmembrane serine protease inhibitors expressed by most epithelial cells. They regulate the pericellular activities of circulating hepatocyte growth factor activator and cellular type II transmembrane serine proteases (TTSPs), proteases required for the activation of hepatocyte growth factor (HGF)/scatter factor (SF). Activated HGF/SF transduces pleiotropic signals through its receptor tyrosine kinase, MET (coded by the proto-oncogene MET), which are necessary for cellular migration, survival, growth and triggering stem cells for accelerated healing. HAI-1 and HAI-2 are also required for normal epithelial functions through regulation of TTSP-mediated activation of other proteases and protease-activated receptor 2, and also through suppressing excess degradation of epithelial junctional proteins. This review summarizes current knowledge regarding the mechanism of pericellular HGF/SF activation and highlights emerging roles of HAIs in epithelial development and integrity, as well as tumorigenesis and progression of transformed epithelial cells.

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Section: Ttsps: Localized Cellular Activators Of Hgf/sf In Epithelialmentioning

confidence: 99%

Hepatocyte growth factor activator inhibitors (HAI‐1 and HAI‐2): Emerging key players in epithelial integrity and cancer

Kataoka

Kawaguchi

Fukushima

et al. 2018

Pathology International

129

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“…As hepsin belongs to the transmembrane type II serine protease superfamily and has also been related with different malignant tumors [ 14 , 15 ], we performed a similar study to evaluate the interaction between hepsin and native or prelatent AT. Unlike the previous case, the results point toward native AT being capable of establishing a covalent complex with hepsin under both reducing and non-reducing conditions.…”

Section: Resultsmentioning

confidence: 99%

“…However, other serine proteases could fall under the control of AT or of its different forms. One example is hepsin, which belongs to the transmembrane type II serine protease superfamily and whose expression has been related with different tumors such as prostate, cervix or gastric cancer [ 14 , 15 ]. AT inherits the structural flexibility of the serpins that enables it to carry out its inhibitory function on its target proteases [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Tumor Functions of Prelatent Antithrombin on Glioblastoma Multiforme Cells

et al. 2021

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Antithrombin, the main physiological inhibitor of the coagulation cascade, exerts anti-tumor effects on glioblastoma multiforme cells. Antithrombin has different conformations: native, heparin-activated, prelatent, latent, and cleaved. The prelatent form has an intermediate affinity between latent and native antithrombin, although it is the most antiangiogenic form. Herein, we investigate the effect of this conformation on the tumorigenic processes of glioblastoma multiforme cells. Antithrombin forms were purified by chromatography. Chromogenic/fluorogenic assays were carried out to evaluate enteropeptidase and hepsin inhibition, two serine proteases involved in these processes. Wound healing, Matrigel invasion and BrdU incorporation assays were performed to study migration, invasion and proliferation. E-cadherin, Vimentin, VEGFA, pAKT, STAT3, pSTAT3, and pERK1/2 expression was assessed by Western blot and/or qRT-PCR. Prelatent antithrombin inhibited both enteropeptidase and hepsin, although it was less efficient than the native conformation. Exposure to prelatent antithrombin significantly reduced migration and invasion but not proliferation of U-87 MG, being the conformation most efficient on migration. Prelatent antithrombin down-regulated VEGFA, pSTAT3, and pERK1/2 expression in U-87 MG cells. Our work elucidates that prelatent antithrombin has surprisingly versatile anti-tumor properties in U-87 MG glioblastoma multiforme cells. This associates with resistance pathway activation, the decreased expression of tumorigenic proteins, and increased angiogenesis, postulating the existence of a new, formerly unknown receptor with potential therapeutic implications.

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“…In a study by Tanimoto et al [17], the effect of hepsin serine protease in patients with ovarian carcinoma showed that hepsin expression increased in patients with ovarian carcinoma. In a study by Zhang et al [18] on patients with gastric carcinoma, high hepsin expression was associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 97%

Determination of galectin-3, hepsin and thyroid transcription factor-1 levels in thyroid cancer patients; A prospective case-control study

Memiş

Karadeniz

Akçay

et al. 2019

Archives of Clinical and Experimental Medicine

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Aim: This study aimed to the efficiacy of usage galectin-3, hepsin, and thyroid transcription factor-1 (TTF-1) levels as markers for the differentiation between patients with malignant and benign thyroid nodules. Methods: The study was done prospectively between January 2018 and April 2018 in our clinic, in patients who were diagnosed with thyroid nodules and scheduled for surgery. Galectin-3, hepsin, and TTF-1 levels were measured in the preoperative serum of the benign and malignant groups. The measured levels were evaluated statistically to determine whether there was any significant difference between the malignant and benign groups. Results: When the levels of galectin-3, hepsin, and TTF-1 in the malignant and benign groups were compared, there was a statistically significant difference in TTF-1 levels (p=0.038). However, no significant difference was found in hepsin and galectin-3. When the macropapillary and micropapillary types were compared within the malignant patient group, there was a significant difference between the galectin-3 levels (p = 0.009), but no difference was found between hepsin and TTF-1. Conclusions: It was seen that the decrease of galectin-3 levels in thyroid papillary carcinoma could be effective in the transformation from microcarcinoma to macrocarcinoma, and TTF-1 could be an important marker for the differentiation between benign and malignant thyroid nodules.

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High Hepsin expression predicts poor prognosis in Gastric Cancer

Cited by 15 publications

References 41 publications

Hepatocyte growth factor activator inhibitors (HAI‐1 and HAI‐2): Emerging key players in epithelial integrity and cancer

Hepatocyte growth factor activator inhibitors (HAI‐1 and HAI‐2): Emerging key players in epithelial integrity and cancer

Anti-Tumor Functions of Prelatent Antithrombin on Glioblastoma Multiforme Cells

Determination of galectin-3, hepsin and thyroid transcription factor-1 levels in thyroid cancer patients; A prospective case-control study

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