Requirement of the enzymatic and signaling activities of plasmin for phorbol-ester-induced scattering of colon cancer cells

Experimental Cell Research
Víctor M DíazRosanna Paciucci

Abstract

Colon cancer progression is associated with the activation of protein kinase C (PKC), the downregulation of functional E-cadherin and an increased expression of the serine protease urokinase (u-PA) and its receptor (u-PAR). HT29-M6 intestinal epithelial cells represent an in vitro model to study colon cancer progression. These cells are induced to scatter and to invade by phorbol esters. Using proteolytic and cell signaling inhibitors, we show that HT29-M6 cells require plasminogen for the acquisition of the scattering response to PMA. Our results indicate that, prior to inducing a state of competency for plasminogen-dependent scattering, PMA triggers an ordered succession of events where upregulation of the activity of u-PA precedes proteolysis of u-PAR and active degradation of the extracellular matrix (ECM). These events poise HT29-M6 cells to a scatter-competent state that allows the subsequent localized proteolytic activation of plasminogen to plasmin, required for the execution of scattering. Finally, we show that, in addition to its enzymatic activity directed at the degradation of ECM, plasmin generates an intracellular signal resulting in the phosphorylation of ERK 1/2. For a full motogenic activity, plasmin requires t...Continue Reading

References

Apr 6, 1987·FEBS Letters·J D Vassalli, D Belin
Apr 1, 1983·The Journal of Investigative Dermatology·R R Isseroff, D B Rifkin
Sep 15, 1994·International Journal of Cancer. Journal International Du Cancer·H SolbergG Høyer-Hansen
Sep 1, 1994·International Journal of Cancer. Journal International Du Cancer·H WangD Boyd
Jan 15, 1997·European Journal of Biochemistry·G Høyer-HansenK Danø
Jun 17, 1998·The Journal of Biological Chemistry·E BatlleA G de Herreros
Oct 6, 1999·Current Opinion in Cell Biology·G Murphy, J Gavrilovic
Nov 29, 2002·Frontiers in Bioscience : a Journal and Virtual Library·Thomas HerrenEdward F Plow
Dec 4, 2002·Nature Reviews. Molecular Cell Biology·Francesco Blasi, Peter Carmeliet
Jan 24, 2003·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Eric J KortJames H Resau
Jul 13, 2004·The Journal of Biological Chemistry·Mousumi MajumdarYoshikazu Takada
Jul 28, 2004·Trends in Immunology·Anna Mondino, Francesco Blasi

❮ Previous
Next ❯

Citations

Apr 3, 2007·BMC Physiology·Ricardo SabanMarcia R Saban
Feb 8, 2008·Reproduction, Fertility, and Development·Thomas PapanikolaouConstantinos A Rekkas
Mar 18, 2010·Cancer Research·Qun WeiZhi-Ping Liu

❮ 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.

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.

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.