The functional activity of E-cadherin controls tumor cell metastasis at multiple steps

Proceedings of the National Academy of Sciences of the United States of America
Tae-Young NaBarry M Gumbiner

Abstract

E-cadherin is a tumor suppressor protein, and the loss of its expression in association with the epithelial mesenchymal transition (EMT) occurs frequently during tumor metastasis. However, many metastases continue to express E-cadherin, and a full EMT is not always necessary for metastasis; also, positive roles for E-cadherin expression in metastasis have been reported. We hypothesize instead that changes in the functional activity of E-cadherin expressed on tumor cells in response to environmental factors is an important determinant of the ability of the tumor cells to metastasize. We find that E-cadherin expression persists in metastatic lung nodules and circulating tumor cells (CTCs) in two mouse models of mammary cancer: genetically modified MMTV-PyMT mice and orthotopically grafted 4T1 tumor cells. Importantly, monoclonal antibodies that bind to and activate E-cadherin at the cell surface reduce lung metastasis from endogenous genetically driven tumors and from tumor cell grafts. E-cadherin activation inhibits metastasis at multiple stages, including the accumulation of CTCs from the primary tumor and the extravasation of tumor cells from the vasculature. These activating mAbs increase cell adhesion and reduce cell invasio...Continue Reading

References

Jul 1, 1994·The Journal of Cell Biology·W M Brieher, B M Gumbiner
Jan 1, 1996·Current Topics in Microbiology and Immunology·M E BrackeM M Mareel
Dec 15, 1996·Developmental Biology·F Fagotto, B M Gumbiner
Sep 8, 1998·Current Opinion in Genetics & Development·B M Gumbiner
Jan 29, 1999·The Journal of Cell Biology·Y ZhongB M Gumbiner
Mar 31, 1999·Trends in Biochemical Sciences·G Christofori, H Semb
May 8, 2000·International Journal of Cancer. Journal International Du Cancer·C Y SasakiA Passaniti
Jan 1, 2003·The Journal of Cell Biology·Alpha S Yap, Eva M Kovacs
Mar 6, 2004·Science·W James Nelson, Roel Nusse
Aug 5, 2004·The Journal of Biological Chemistry·Stéphane FouquetSophie Thenet
Aug 5, 2006·Breast Cancer Research : BCR·Anna Fantozzi, Gerhard Christofori
Sep 6, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Yuanmei LouShoukat Dedhar
Feb 26, 2010·Cold Spring Harbor Perspectives in Biology·Julian Heuberger, Walter Birchmeier
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nam-Gyun KimBarry M Gumbiner
Oct 18, 2011·Cell·Scott Valastyan, Robert A Weinberg
Apr 17, 2012·International Journal of Cell Biology·Yong-Nyun KimHyeryeong Kim
Apr 20, 2012·Molecular Biology of the Cell·Yuliya I PetrovaBarry M Gumbiner
Jan 23, 2013·Breast Cancer Research and Treatment·Antoinette HollestelleJohn W M Martens
Feb 18, 2014·Journal of Cell Science·Barry M Gumbiner, Nam-Gyun Kim
Mar 5, 2014·The Journal of Cell Biology·Eliah R ShamirAndrew J Ewald
Jul 16, 2015·The Journal of Biological Chemistry·Nitesh ShashikanthDeborah E Leckband
Apr 29, 2016·Science·Kevin J Cheung, Andrew J Ewald
Nov 2, 2016·Molecular Biology of the Cell·Yuliya I PetrovaBarry M Gumbiner
Oct 21, 2017·Genes & Development·Douglas S MicalizziDaniel A Haber
May 22, 2018·Oncogene·Alisha M MendonsaBarry M Gumbiner
Sep 6, 2019·Nature·Veena PadmanabanAndrew J Ewald

❮ Previous
Next ❯

Citations

Oct 2, 2020·Breast Cancer Research and Treatment·Shunchao YanBenita S Katzenellenbogen
Jul 28, 2020·International Journal of Molecular Sciences·Han-A ParkYonghyun Kim
Aug 28, 2020·The New England Journal of Medicine·Lorraine O'Driscoll
Dec 10, 2020·Metallomics : Integrated Biometal Science·Debora WernitznigBernhard K Keppler
Feb 13, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Ki-Sook ParkBarry M Gumbiner
Feb 19, 2021·Pathology, Research and Practice·Zhi Xiong ChongWan Yong Ho
Apr 10, 2021·Cell Communication and Signaling : CCS·Sang R LeeEui-Ju Hong
May 6, 2021·Clinical & Experimental Metastasis·S David NathansonKevin Cheung
Jul 6, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Smita KumariPravir Kumar
Jul 14, 2021·Clinical & Experimental Metastasis·Emma WrennKevin Cheung
Aug 24, 2021·Frontiers in Molecular Biosciences·Huichen ZhaoXiao-Bing Chen
Mar 9, 2021·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Anuka SharmaShalmoli Bhattacharyya

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Biophysics of Adhesion

Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. It is also essential for infectious organisms, such as bacteria or viruses, to cause diseases. Understanding the biophysics of cell adhesion can help understand these diseases. Discover the latest research on the biophysics of adhesion here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Related Papers

Molecular Biology of the Cell
Yuliya I PetrovaBarry M Gumbiner
Journal of Mammary Gland Biology and Neoplasia
C L Sommers
Biochimica Et Biophysica Acta
Fausto RodriguezPanos Z Anastasiadis
© 2021 Meta ULC. All rights reserved