Involvement of stromal p53 in tumor-stroma interactions

Jair Bar, Neta Moskovits, Moshe Oren*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


p53 is a major tumor-suppressor gene, inactivated by mutations in about half of all human cancer cases, and probably incapacitated by other means in most other cases. Most research regarding the role of p53 in cancer has focused on its ability to elicit apoptosis or growth arrest of cells that are prone to become malignant owing to DNA damage or oncogene activation, i.e. cell-autonomous activities of p53. However, p53 activation within a cell can also exert a variety of effects upon neighboring cells, through secreted factors and paracrine and endocrine mechanisms. Of note, p53 within cancer stromal cells can inhibit tumor growth and malignant progression. Cancer cells that evolve under this inhibitory influence acquire mechanisms to silence stromal p53, either by direct inhibition of p53 within stromal cells, or through pressure for selection of stromal cells with compromised p53 function. Hence, activation of stromal p53 by chemotherapy or radiotherapy might be part of the mechanisms by which these treatments cause cancer regression. However, in certain circumstances, activation of stromal p53 by cytotoxic anti-cancer agents might actually promote treatment resistance, probably through stromal p53-mediated growth arrest of the cancer cells or through protection of the tumor vasculature. Better understanding of the underlying molecular mechanisms is thus required. Hopefully, this will allow their manipulation towards better inhibition of cancer initiation, progression and metastasis.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalSeminars in Cell and Developmental Biology
Issue number1
StatePublished - Feb 2010
Externally publishedYes


FundersFunder number
National Cancer Institute
Flight Attendant Medical Research Institute
Seventh Framework Programme201102
European Commission
Robert Bosch Stiftung
Seventh Framework Programme
Sixth Framework Programme502983


    • Cancer
    • Cancer-associated-fibroblasts
    • SDF-1
    • Stroma
    • p53


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