Extracellular Matrix, Nuclear and Chromatin Structure, and Gene Expression in Normal Tissues and Malignant Tumors: A Work in Progress

Virginia A. Spencer, Ren Xu, Mina J. Bissell

Research output: Contribution to journalReview articlepeer-review

65 Scopus citations

Abstract

Almost three decades ago, we presented a model where the extracellular matrix (ECM) was postulated to influence gene expression and tissue-specificity through the action of ECM receptors and the cytoskeleton. This hypothesis implied that ECM molecules could signal to the nucleus and that the unit of function in higher organisms was not the cell alone, but the cell plus its microenvironment. We now know that ECM invokes changes in tissue and organ architecture and that tissue, cell, nuclear, and chromatin structure are changed profoundly as a result of and during malignant progression. Whereas some evidence has been generated for a link between ECM-induced alterations in tissue architecture and changes in both nuclear and chromatin organization, the manner by which these changes actively induce or repress gene expression in normal and malignant cells is a topic in need of further attention. Here, we will discuss some key findings that may provide insights into mechanisms through which ECM could influence gene transcription and how tumor cells acquire the ability to overcome these levels of control.

Original languageEnglish
Pages (from-to)275-294
Number of pages20
JournalAdvances in Cancer Research
Volume97
DOIs
StatePublished - 2007

Bibliographical note

Funding Information:
Our work was supported by grants from the Office of Biological and Environmental Research of the Department of Energy (DE‐AC03‐76SF00098), the National Cancer Institute (CA057621‐13 to Zena Werb and M.J.B.), the Department of Defense Breast Cancer Research Program (Innovator Award DAMD17‐02‐1‐438 to M.J.B., and postdoctoral fellowships W81XWH0410581 to V.A.S. and DAMD17‐02‐1‐0441 to R.X.), and a postdoctoral fellowship from the Canadian Institute for Health Research to V.A.S.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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