Differential subcellular localization renders HAI-2 a matriptase inhibitor in breast cancer cells but not in mammary epithelial cells

PloS One
Hsiang-Hua D ChangChen-Yong Lin

Abstract

The type 2 transmembrane serine protease matriptase is under tight control primarily by the actions of the integral membrane Kunitz-type serine protease inhibitor HAI-1. Growing evidence indicates that HAI-2 might also be involved in matriptase inhibition in some contexts. Here we showed that matriptase inhibition by HAI-2 depends on the subcellular localizations of HAI-2, and is observed in breast cancer cells but not in mammary epithelial cells. HAI-2 is co-expressed with matriptase in 21 out of 26 human epithelial and carcinoma cells examined. 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. Induction of matriptase zymogen activation in mammary epithelial cells results in the formation of matriptase-HAI-1 complexes, but matriptase-HAI-2 complexes are not observed. In breast cancer cells, however, in addition to the appearance of matriptase-HAI-1 complex, three different matriptase-HAI-2 complexes, are formed following the induction of matriptase activation. Immunofluorescent staining reveals that activated matriptase is focused at the cell-cell junctions upon the induction of m...Continue Reading

References

May 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J BartekJ Taylor-Papadimitriou
Apr 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·M R Stampfer, J C Bartley
Nov 1, 1995·Archives of Otolaryngology--head & Neck Surgery·C H SnydermanD E Eibling
May 1, 1994·International Journal of Cancer. Journal International Du Cancer·S YasumuraT L Whiteside
Mar 7, 1997·The Journal of Biological Chemistry·T ShimomuraN Kitamura
Jan 17, 2002·The Journal of Biological Chemistry·Christelle BenaudChen-Yong Lin
Dec 25, 2002·Clinical & Experimental Metastasis·Christelle M BenaudChen-Yong Lin
May 10, 2003·The Journal of Biological Chemistry·Michael D OberstChen-Yong Lin
Jul 23, 2003·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Michael D OberstChen-Yong Lin
Apr 1, 2005·American Journal of Physiology. Cell Physiology·Michael D OberstChen-Yong Lin
Feb 3, 2009·American Journal of Human Genetics·Peter Heinz-ErianAndreas R Janecke
Jun 19, 2009·American Journal of Physiology. Cell Physiology·Jehng-Kang WangChen-Yong Lin
Nov 27, 2009·The Journal of Biological Chemistry·I-Chu TsengChen-Yong Lin
Nov 26, 2010·Cancer Research·Carolyn V UstachHyeong-Reh Choi Kim
Oct 5, 2011·Journal of Medicinal Chemistry·Zhenghong XuChen-Yong Lin
Oct 28, 2011·American Journal of Physiology. Cell Physiology·Han XuChen-Yong Lin
Sep 28, 2013·The American Journal of Pathology·Feng-Pai ChouChen-Yong Lin

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Citations

Feb 20, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Yi-Lin ChiuChen-Yong Lin
Dec 21, 2018·Journal of Medicinal Chemistry·Vishnu C DamalankaJames W Janetka

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Methods Mentioned

BETA
immunodepletion
protein assay

Software Mentioned

ImageJ

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