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Semin Cancer Biol. 2019 Sep 9. pii: S1044-579X(18)30173-1. doi: 10.1016/j.semcancer.2019.09.003. [Epub ahead of print]

Cell competition and tumor heterogeneity.

Author information

1
Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal; Departments of Surgery, Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
2
Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal.
3
Departments of Surgery, Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA; VA Roudebush Medical Center, Indianapolis, IN, 46202, USA. Electronic address: hnakshat@iupui.edu.
4
Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal. Electronic address: rajan.gogna@research.fchampalimaud.org.

Abstract

Cancers exhibit a remarkable degree of intratumoral heterogeneity (ITH), which results from complex cellular interactions amongst various cell types. This phenomenon provides an opportunity for clonal selection and growth advantages to aggressive cancer cell types, resulting in worse prognosis and challenges to anti-cancer therapy. Cell competition is a conserved mechanism operational in cellular and organ systems, which allows neighboring cells to compare their relative fitness levels and results in the elimination of viable but suboptimal cells. By abuse of this conserved homeostasis mechanism, aggressive cancer cell types gain an advantage over normal cell types by achieving traits like increased proliferation, de-differentiation, and stemness. This review presents recent evidence that cell competition mechanisms actively participate in the regulation of intratumoral cell-cell interactions and thus contribute to ITH, and this process is essential for cancer development and progression.

KEYWORDS:

Cancer; Cell competition; Epithelial mesenchymal transition; Myc; Oncogenic pathways; Tumour heterogeneity; Tumour microenvironment; p53

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