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The stemness of cancer cells
Date:12/14/2010

the tumor cell population expands, so goes the prevailing theory, individual cells pick up random mutations, and their molecular identity starts to diverge. By the time the cancer is detected, the millions of cells that make up the tumor have become as different from each other as third cousins twice removed.

There had also been a longstanding notion that fully committed and specialized cells might de-differentiate over the course of tumor initiation and progression, although it was unclear how this might be achieved. Eventually the theory was discarded in favor of the currently fashionable cancer stem cell theory, which holds that cancer stem cells-the cells that propagate a tumor and that could potentially arise from normal stem or early progenitors-are distinct from the bulk of the cancer cells in that they can self-renew as well as produce non-stem cells, just as normal stem cells do.

"Our findings indicate that cancer cells that resemble stem cells need not be part of the original tumor but rather may emerge during later stages of tumor development, facilitated by the loss of p53," says postdoctoral researcher and co-first author Benjamin T. Spike, Ph.D. "The observed tumor heterogeneity is probably a combination of growing genomic instability and epigenetic instability associated with the acquisition of a stem cell-like phenotype."

Wahl and his team first considered the possibility that p53 does more then function as a "genome guardian" when a collaborative study with Juan Carlos Izpisa Belmonte, Ph.D., also a professor in the Gene Expression Laboratory at the Salk Institute, revealed that this tumor suppressor also presents a barrier to somatic cell reprogramming.

To find out whether p53 inactivation does permit the emergence of tumor cells resembling stem cells, Spike and Mizuno combed through hundreds of archival gene expression profiles of breast and lung tumors, searching for stem cell-like signatures and correlating t
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Contact: Gina Kirchweger
858-453-410-01340
Salk Institute
Source:Eurekalert  

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