Cell Growth & Differentiation, Vol 9, Issue 11 905-918, Copyright © 1998 by American Association of Cancer Research

ARTICLES

Identification of a novel mechanism of regulation of the adherens junction by E1A, Rac1, and cortical actin filaments that contributes to tumor progression

RS Fischer and MP Quinlan
Department of Microbiology & Immunology, University of Tennessee Health Science Center, Memphis 38163, USA.

Transformation progression toward more malignant behavior often results from a loss of epithelial cell behavior, especially cell-cell adhesion. E1A cooperates with ras to transform primary epithelial cells such that they maintain epithelial cell differentiation, including the proper localization of adherens junctions (AJs). Second exon mutants of E1A 12S cooperate with ras to produce a more aggressively transformed phenotype, termed hypertransformation, that includes the loss of adhesion. Such hypertransformation can also be achieved by the addition of activated Rac1 to cells expressing wild-type E1A and ras, suggesting that actin reorganization may be important for the hypertransformed phenotype. Primary epithelial cells expressing hypertransforming mutants of E1A or V12Rac1 exhibit the loss of cortical actin filaments. In these cells, AJ complexes do not incorporate alpha-catenin, fail to associate with the cytoskeleton, and fail to localize to the plasma membrane, resulting in the destabilization of the AJ components and a loss of function. Loss of these epithelial cell characteristics predisposes these cells to a more malignant phenotype due to the loss of cell-cell adhesion. Taken together, these results suggest a novel mechanism of regulation of AJ function in tumor progression that involves the correct targeting of the AJ components, and this is affected by the status of cortical actin, which can be differentially affected by E1A or Rac1.

This article has been cited by other articles:

				H. Reuveni, T. Geiger, B. Geiger, and A. Levitzki Reversal of the Ras-Induced Transformed Phenotype by Hr12, a Novel Ras Farnesylation Inhibitor, Is Mediated by the Mek/ERK Pathway J. Cell Biol., December 11, 2000; 151(6): 1179 - 1192. [Abstract] [Full Text] [PDF]

				M. P. Quinlan and J. L. Hyatt Establishment of the Circumferential Actin Filament Network Is a Prerequisite for Localization of the Cadherin-Catenin Complex in Epithelial Cells Cell Growth Differ., December 1, 1999; 10(12): 839 - 854. [Abstract] [Full Text]

				K. W. Foster, S. Ren, I. D. Louro, S. M. Lobo-Ruppert, P. McKie-Bell, W. Grizzle, M. R. Hayes, T. R. Broker, L. T. Chow, and J. M. Ruppert Oncogene Expression Cloning by Retroviral Transduction of Adenovirus E1A-immortalized Rat Kidney RK3E Cells: Transformation of a Host with Epithelial Features by c-MYC and the Zinc Finger Protein GKLF Cell Growth Differ., June 1, 1999; 10(6): 423 - 434. [Abstract] [Full Text]

				F. Scholl, C Gamallo, S Vilar?o, and M Quintanilla Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes J. Cell Sci., January 12, 1999; 112(24): 4601 - 4613. [Abstract] [PDF]