PTHrP promotes colon cancer cell migration and invasion in an integrin α6β4-dependent manner through activation of Rac1.

Cancer Letters
Ramanjaneya V R MulaMiriam Falzon

Abstract

Parathyroid hormone-related protein (PTHrP) is expressed by human colon cancer tissue and cell lines. Rac1 GTPase enhances colon cancer cell migration and invasion. Here we report a positive correlation between PTHrP expression and Rac1 activity in LoVo (human colon cancer) cells. The positive effects of PTHrP on Rac1 activity and on cell migration and invasion are mediated via the guanine nucleotide exchange factor Tiam1. Knockdown of integrin α6β4, which is upregulated by PTHrP, negates the PTHrP-mediated increase in Rac1 activation. Integrin α6β4 signals synergistically with growth factor receptors to activate the phosphatidylinositol 3-kinase (PI3-K) pathway. Chemical inhibition of PI3-K negates the PTHrP-mediated effects on Tiam1 and Rac1 activity. Tumors from PTHrP-overexpressing LoVo cells also show increased expression of Tiam1. Taken together, these observations provide evidence of a link between PTHrP and Rac1 activity through integrin α6β4, resulting in enhanced cell migration and invasion. Targeting PTHrP production in colon cancer may thus prove therapeutically beneficial.

References

May 25, 1995·Nature·F MichielsJ G Collard
Feb 9, 1996·Cell·D A Lauffenburger, A F Horwitz
Feb 9, 1996·Cell·T J Mitchison, L P Cramer
Jan 1, 1996·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·E Strunck, G Vollmer
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Nov 18, 2000·Experimental Cell Research·A A SchmitzL Van Aelst
Apr 27, 2001·Seminars in Cancer Biology·A M Mercurio, I Rabinovitz
Mar 15, 2003·Nature Reviews. Cancer·Erik Sahai, Christopher J Marshall
Feb 11, 2004·Cellular and Molecular Life Sciences : CMLS·E Maioli, V Fortino
Mar 5, 2004·Breast Cancer Research and Treatment·Meghan E MinardGary E Gallick
Mar 17, 2004·Seminars in Cancer Biology·Paul M Campbell, Channing J Der
Mar 17, 2004·Journal of Cell Science·Krister Wennerberg, Channing J Der
Oct 2, 2004·Nature Reviews. Molecular Cell Biology·Wenjun Guo, Filippo G Giancotti
Jan 19, 2005·World Journal of Gastroenterology : WJG·Li LiuYan-Qing Ding
Mar 12, 2005·CA: a Cancer Journal for Clinicians·D Max ParkinPaola Pisani
May 14, 2005·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Teresa Gómez del PulgarJuan Carlos Lacal
Dec 27, 2005·Current Opinion in Genetics & Development·Bradford W OzanneRobert F Hennigan
Jan 18, 2006·Cellular and Molecular Life Sciences : CMLS·L Kopfstein, G Christofori
Jan 24, 2007·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Jan 1, 2008·The American Journal of Pathology·Carolina EspinaJuan Carlos Lacal

❮ Previous
Next ❯

Citations

Mar 5, 2013·Journal of Translational Medicine·Pu LiKeke Huo
Jul 27, 2012·Future Oncology·Fabiana N SokiLaurie K McCauley
Oct 4, 2015·Developmental Biology·Jiarong LiArthur M Mercurio
Dec 6, 2014·Breast Cancer Research and Treatment·Terri Patricia McVeighNicola Miller
Aug 27, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Veronika RamovsArnoud Sonnenberg
Jun 23, 2015·Cancers·Miriam Falzon, Vandanajay Bhatia
Jul 19, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Vandanajay BhatiaMiriam Falzon
Apr 16, 2020·International Journal of Molecular Sciences·Matthew KirkhamJared J Barrott
Sep 28, 2013·Molecular Cancer Therapeutics·Hemant K BidPeter J Houghton

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

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.

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.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.