Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 846K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, R. Search for Related Content PubMed Articles by Williams, R. Related Collections Related Article Social Bookmarking                            What's this?

Tension testing in adherent cells

p66Shc checks the cell's anchor points (yellow) to ensure a good grip.

Like soloing rock climbers, adherent cells need a good handhold to survive. Ma et al. now identify an adaptor protein that monitors the cell's grip and signals death if the grip fails.

Death following detachment, known as anoikis, is a form of programmed cell death that ensures the disposal of displaced adherent cells. Lack of anoikis is thought to give cells metastatic potential.

A number of survival factors have been identified that are activated by integrin attachment to the extracellular matrix. Binding to soluble matrix fragments, rather than to a fixed matrix, does not prevent anoikis. This difference suggests that mechanical tension is also being measured.

Inside the cell, integrins associate with signaling adaptor proteins of the Shc family. One family member, p66^Shc, has been suggested to promote apoptosis. The team now shows that an epithelial cell line that resists anoikis does not express p66^Shc. Giving these cells back some p66^Shc reestablished detachment-induced death. Normal epithelial and endothelial cells express p66^Shc. Thus, p66^Shc must only trigger death upon cell detachment.

p66^Shc did not induce anoikis by the same mechanism as it induces apoptosis. For apoptosis, p66^Shc enters mitochondria. But for anoikis, p66^Shc associated with integrins and activated the actin cytokeleton regulator RhoA.

RhoA increases tension between cell attachment points by inducing stress fiber formation. Inhibiting contraction of these fibers, the team showed, curbed anoikis. The authors therefore suggest that the cell continuously checks its tension by contracting its stress fibers—like checking from the inside of a tent whether the pegs are secure. If the cell contracts easily, then p66^Shc signals that external anchors are missing and that, for this cell, the camping trip is over.

Reference:

Ma, Z., et al. 2007. J. Cell Biol. 179:23–31.[Abstract/Free Full Text]

Ruth Williams

ruth.williams{at}rockefeller.edu

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

p66^Shc mediates anoikis through RhoA

Zhenyi Ma, David P. Myers, Ru Feng Wu, Fiemu E. Nwariaku, and Lance S. Terada
J. Cell Biol. 2007 179: 23-31. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 846K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, R. Search for Related Content PubMed Articles by Williams, R. Related Collections Related Article Social Bookmarking                            What's this?