Cortactin affects cell migration by regulating intercellular adhesion and cell spreading

Experimental Cell Research
Agnes G S H van RossumEd Schuuring

Abstract

Cortactin is an F-actin binding protein that stabilizes F-actin networks and promotes actin polymerization by activating the Arp2/3 complex. Overexpression of cortactin, as observed in several human cancers, stimulates cell migration, invasion, and experimental metastasis; however, the underlying mechanism is not understood. To investigate the importance of cortactin in cell migration, we downregulated its expression using RNA interference (RNAi). Stable downregulation of cortactin in HBL100 breast epithelial cells resulted in (i) decreased cell migration and invasion, (ii) enhanced cell-cell adhesion, and (iii) accelerated cell spreading. These phenotypic changes were reversed by expression of RNAi-resistant mouse cortactin. Cortactin colocalized with cadherin and beta-catenin in adherens junctions, consistent with its role in intercellular adhesion. Remarkably, cortactin deficiency did not affect lamellipodia formation. Instead, downregulation of cortactin in human squamous carcinoma cells that overexpress cortactin changed the cytoskeletal organization. We conclude that increased levels of cortactin, as found in human carcinomas, promote cell migration and invasion by reducing cell spreading and intercellular adhesive strength.

References

Oct 1, 1991·Molecular and Cellular Biology·H WuJ T Parsons
Jan 1, 1982·Cell and Tissue Research·E V Gaffney
Nov 3, 1995·The Journal of Biological Chemistry·H Okamura, M D Resh
Jan 1, 1995·Cell Motility and the Cytoskeleton·K HiuraM Sato
Nov 15, 1996·International Journal of Cancer. Journal International Du Cancer·D H CampbellR J Daly
Feb 21, 1998·Current Biology : CB·S M van HamJ Neefjes
Sep 25, 1998·The Journal of Biological Chemistry·C HuangX Zhan
Oct 29, 1998·The Journal of Biological Chemistry·T KatsubeS Togashi
Nov 21, 1998·Cell Adhesion and Communication·E SchuuringP Kluin
Dec 19, 1998·Microscopy Research and Technique·E A Cox, A Huttenlocher
Mar 27, 2001·Current Biology : CB·A M WeaverJ A Cooper
Oct 19, 2001·Oncogene·S A Weed, J T Parsons
Jan 10, 2002·Biochimica Et Biophysica Acta·U Cavallaro, G Christofori
Mar 23, 2002·Science·Thijn R BrummelkampReuven Agami
Aug 15, 2002·Current Biology : CB·Alissa M WeaverJohn A Cooper
Nov 7, 2002·Current Biology : CB·Dorothy A SchaferJohn A Cooper
Dec 11, 2002·The Journal of Cell Biology·Kris A DeMaliKeith Burridge
Jan 9, 2003·Current Opinion in Cell Biology·Alissa M WeaverJohn A Cooper
Feb 5, 2003·Biochemical and Biophysical Research Communications·Setsuko Mise-OmataOreste Acuto
Mar 4, 2003·Molecular and Cellular Biology·Hong CaoMark A McNiven
Mar 7, 2003·Current Biology : CB·Andrew W KinleyJ Thomas Parsons
Jun 10, 2003·International Journal of Cancer. Journal International Du Cancer·Linda A GordonJ Louise Jones
Sep 4, 2003·The Journal of Biological Chemistry·Agnes G S H van RossumEd Schuuring
Nov 13, 2003·Current Opinion in Plant Biology·Michael J Deeks, Patrick J Hussey
Dec 6, 2003·Science·Anne J RidleyAlan Rick Horwitz
Dec 17, 2003·Journal of Cell Science·Gerald Burgstaller, Mario Gimona
Jan 7, 2004·Mechanisms of Development·Kálmán Somogyi, Pernille Rørth
Mar 3, 2004·Biochemistry·Kyoungtae KimJohn A Cooper
Mar 17, 2004·The Journal of Cell Biology·Falak M HelwaniAlpha S Yap
Mar 20, 2004·The Biochemical Journal·Lingzhi FanAndrás Kapus
May 26, 2004·The Journal of Biological Chemistry·Suzie VermaAlpha S Yap
Jun 10, 2004·The Biochemical Journal·Roger J Daly

❮ Previous
Next ❯

Citations

Apr 4, 2014·World Journal of Gastroenterology : WJG·Jun WeiTian-Geng You
Jun 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Shlomit BoguslavskyAlexander Bershadsky
Sep 22, 2007·The Journal of Clinical Investigation·Jing ZhangGary E Gallick
Jul 11, 2009·The Journal of Biological Chemistry·Jesús García-CastilloJoaquín Arribas
Feb 17, 2009·World Journal of Urology·Giueng-Chueng WangJong-Shiaw Jin
Nov 19, 2015·Journal of Cellular Physiology·Gaofeng ZhangBing Song
Aug 9, 2011·The International Journal of Biochemistry & Cell Biology·Melanie MartiniKlaus-Peter Janssen
Mar 23, 2011·Human Pathology·Eliane Papa AmbrosioSilvia Regina Rogatto
Jan 8, 2008·Experimental Cell Research·Hugh KimChristopher A McCulloch
Jun 6, 2015·Biochemical and Biophysical Research Communications·Alan HammerMaria Diakonova
Jul 22, 2009·Genesis : the Journal of Genetics and Development·Shinji TanakaShigeo Okabe
Sep 3, 2009·Microscopy Research and Technique·María Leiza VitaleR-Marc Pelletier
Feb 28, 2009·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Chih-Kung LinJong-Shiaw Jin
Jul 11, 2008·Cell Motility and the Cytoskeleton·Amanda Gatesman Ammer, Scott A Weed
Oct 4, 2012·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Wen-Chiuan TsaiJong-Shiaw Jin
Jan 4, 2012·Histopathology·Chih-Kung LinDueng-Yuan Hueng
Apr 15, 2008·Cancer Letters·Alissa M Weaver
Aug 4, 2015·Annals of Surgical Treatment and Research·Dae Yong KimJeong Kyun Lee
Jan 25, 2011·Cell Adhesion & Migration·Kellye C KirkbrideAlissa M Weaver
Jan 3, 2012·International Journal of Radiation Oncology, Biology, Physics·Michiel L SchrijversE Schuuring
Mar 10, 2012·Journal of the Korean Surgical Society·Seok Youn LeeSoo Cheon Chae
Feb 14, 2014·PloS One·Jan BlancatoSusette C Mueller
May 19, 2007·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Wen-Chiuan TsaiYou-Chen Chao
Feb 13, 2008·British Journal of Cancer·J H GibcusJ E van der Wal
Jun 10, 2010·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·Jian-hua CaiZheng-gang Zhu
Sep 23, 2006·Physiology·Laura I Cosen-Binker, András Kapus
Nov 21, 2017·Oncotarget·Miao YinLiguo An
Mar 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Deborah A Klos DehringJanis K Burkhardt
Nov 28, 2017·Small GTPases·Pauline Jeannot, Arnaud Besson
Apr 15, 2008·Experimental Biology and Medicine·Candida N PereraIgnacio G Camarillo
Mar 10, 2016·International Journal of Molecular Medicine·Hao-Cheng LongJia-Rui Feng
Nov 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Johan H GibcusEd Schuuring
Nov 3, 2020·BioMed Research International·Shisan LiuYanhong Yu

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

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.

Actin-binding Proteins

Actin-binding proteins are a component of the actin cytoskeleton that play essential roles in cellular functions such as regulation of actin polymerization, maintenance of cell polarity, gene expression regulation, cell motility and many more functions. Discover the latest research on actin-binding proteins 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.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

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.

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.

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.