αE-catenin is a candidate tumor suppressor for the development of E-cadherin-expressing lobular-type breast cancer

The Journal of Pathology
Jolien S de GrootPatrick W B Derksen

Abstract

Although mutational inactivation of E-cadherin (CDH1) is the main driver of invasive lobular breast cancer (ILC), approximately 10-15% of all ILCs retain membrane-localized E-cadherin despite the presence of an apparent non-cohesive and invasive lobular growth pattern. Given that ILC is dependent on constitutive actomyosin contraction for tumor development and progression, we used a combination of cell systems and in vivo experiments to investigate the consequences of α-catenin (CTNNA1) loss in the regulation of anchorage independence of non-invasive breast carcinoma. We found that inactivating somatic CTNNA1 mutations in human breast cancer correlated with lobular and mixed ducto-lobular phenotypes. Further, inducible loss of α-catenin in mouse and human E-cadherin-expressing breast cancer cells led to atypical localization of E-cadherin, a rounded cell morphology, and anoikis resistance. Pharmacological inhibition experiments subsequently revealed that, similar to E-cadherin-mutant ILC, anoikis resistance induced by α-catenin loss was dependent on Rho/Rock-dependent actomyosin contractility. Finally, using a transplantation-based conditional mouse model, we demonstrate that inducible inactivation of α-catenin instigates acqui...Continue Reading

References

Jan 24, 1998·The Journal of Biological Chemistry·R B HazanD L Rimm
Apr 16, 1998·Nature·P GuilfordA E Reeve
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Sep 12, 2000·Nature Cell Biology·P Z AnastasiadisA B Reynolds
Dec 3, 2003·Nature Cell Biology·Agnieszka KobielakElaine Fuchs
Jul 19, 2006·The Journal of Cell Biology·Dana M PironeChristopher S Chen
Jan 5, 2007·Journal of Medicinal Chemistry·Krista B GoodmanDennis Lee
Aug 4, 2007·Experimental Cell Research·Kiran BhadrirajuChristopher S Chen
Oct 20, 2007·Seminars in Cancer Biology·Jacqueline M Benjamin, W James Nelson
Mar 28, 2008·Biochemical Society Transactions·W James Nelson
Nov 19, 2008·The Journal of Cell Biology·Edwin SotoPanos Z Anastasiadis
May 22, 2009·The Journal of Biological Chemistry·Saumendra BajpaiDenis Wirtz
Sep 19, 2009·Breast Cancer Research and Treatment·Antoinette HollestelleMieke Schutte
Feb 19, 2010·Nature·Graham R BignellMichael R Stratton
May 12, 2010·Cold Spring Harbor Perspectives in Biology·Wenxiang Meng, Masatoshi Takeichi
Jul 13, 2011·The Journal of Clinical Investigation·Ron C J SchackmannPatrick W B Derksen
Sep 23, 2011·Molecular Biology of the Cell·Regina B TroyanovskySergey M Troyanovsky
Dec 5, 2012·The Journal of Pathology·Ian J MajewskiRené Bernards
Aug 21, 2013·Journal of Cell Science·Ron C J SchackmannPatrick W B Derksen
Oct 10, 2015·Cell·Giovanni CirielloCharles M Perou
Feb 24, 2016·Nature Genetics·Hikmat A Al-AhmadieDavid B Solit
Jul 15, 2016·Journal of Mammary Gland Biology and Neoplasia·Milou TenhagenPatrick W B Derksen
Jan 18, 2017·Cold Spring Harbor Perspectives in Biology·René Marc Mège, Noboru Ishiyama
May 17, 2017·Cold Spring Harbor Perspectives in Biology·Heather C Bruner, Patrick W B Derksen

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Citations

Dec 6, 2018·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Patrick R BenusiglioFlorence Coulet
Dec 29, 2020·Cancer Management and Research·Qiang ChiGuang Ma
May 1, 2021·Cancers·Amy E McCart ReedPeter T Simpson
May 11, 2021·Frontiers in Oncology·Yuanyuan QinHongmei Wu
Jun 7, 2021·Biomarker Research·Eike BurandtChristian Bernreuther
Jun 12, 2021·Head and Neck Pathology·Li LeiGerald Berry
May 17, 2021·Molecular & Cellular Proteomics : MCP·Sophie HonederRuth Birner-Gruenberger
Dec 11, 2021·The Journal of Pathology. Clinical Research·Matthias ChristgenHans Kreipe

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