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Mutant p53—a potential player in shaping the tumor–stroma crosstalk
Yan Stein1, Ronit Aloni-Grinstein 1,2, and Varda Rotter 1,*
1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel
2 Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Box 19, Ness Ziona 7410001, Israel
*Correspondence to:Varda Rotter, E-mail: varda.rotter@weizmann.ac.il
J Mol Cell Biol, Volume 11, Issue 7, July 2019, Pages 600-604  https://doi.org/10.1093/jmcb/mjz071
Keyword: mutation oncogenes stromal cells neoplasms tumor progression tumorigenesis molecule tumor microenvironment
A plethora of studies suggest that the non-transformed cellular and non-cellular components of the tumor, collectively known as the tumor microenvironment, have a significant impact on the tumorigenic process. It was suggested that the microenvironment, which initially restricts tumor development, is recruited by the tumor and maintains a crosstalk that further promotes cancer progression. Indeed, many of the molecules that participate in the tumor–stroma crosstalk have been characterized. However, the crucial factors that are responsible for the initiation of this crosstalk or the ‘recruitment’ process remain poorly understood. We propose that oncogenes themselves may influence the ‘recruitment’ of the stromal cells, while focusing on mutant p53. Apart from losing its tumor-suppressing properties, mutant p53 gains novel oncogenic functions, a phenomenon dubbed mutant p53 gain of function (GOF). Here, we discuss possible ways in which mutant p53 may modulate the microenvironment in order to promote tumorigenesis. We thus propose that mutant p53 may serve as a key player in the modulation of the tumor–stroma crosstalk in a way that benefits the tumor. Further elucidation of these ‘recruitment’ processes, dictated by mutant p53, may be utilized for tailoring personalized therapeutic approaches for patients with tumors that harbor p53 mutation.