# Tensional homeostasis and the malignant phenotype

Source: https://onco.cc/key-papers/paper-paszek-cancer-cell/  
OnCo record `paper-paszek-cancer-cell` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one term page, indexed on Europe PMC as PubMed record 16169468 and published in Cancer Cell; the citing page links this DOI, which is how the record was matched.

## Summary

Tumors are stiffer than normal tissue, and tumors have altered integrins. Because integrins are mechanotransducers that regulate cell fate, we asked whether tissue stiffness could promote malignant behavior by modulating integrins. We found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation. Matrix stiffness perturbs epithelial morphogenesis by clustering integrins to enhance ERK activation and increase ROCK-generated contractility and focal adhesions. Contractile, EGF-transformed epithelia with elevated ERK and Rho activity could be phenotypically reverted to tissues lacking focal adhesions if Rho-generated contractility or ERK activity was decreased. Thus, ERK and Rho constitute part of an integrated mechanoregulatory circuit linking matrix stiffness to cytoskeletal tension through integrins to regulate tissue phenotype.

Indexed on Europe PMC as PubMed record 16169468 (DOI 10.1016/j.ccr.2005.08.010). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Cancer Cell
- Year: 2005
- DOI: 10.1016/j.ccr.2005.08.010
- Authors: Paszek MJ, Zahir N, Johnson KR, et al.
- What it means: One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Cancer Cell 2005: https://doi.org/10.1016/j.ccr.2005.08.010
- PubMed: https://pubmed.ncbi.nlm.nih.gov/16169468/
- Europe PMC: https://europepmc.org/article/MED/16169468

## Connected records

- terms: [Mechanical theory: stiffness, pressure and force as causes](https://onco.cc/terms/mechanical-theory-of-cancer/)
- journals: [Cancer Cell](https://onco.cc/journals/cancer-cell/)

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