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Review
. 2021 Jan 7;22(2):518.
doi: 10.3390/ijms22020518.

Cell Fitness: More Than Push-Ups

Adam James Ferrari  1   2   3 , Ronny Drapkin  1   2   4 , Rajan Gogna  5
Affiliations
Review

Cell Fitness: More Than Push-Ups

Adam James Ferrari et al. Int J Mol Sci. .

Abstract

Cell competition (CC) is a feature that allows tumor cells to outcompete and eliminate adjacent cells that are deemed less fit. Studies of CC, first described in Drosophila melanogaster, reveal a diversity of underlying mechanisms. In this review, we will discuss three recent studies that expand our understanding of the molecular features governing CC. In particular, we will focus on a molecular fitness fingerprint, oncogenic pathways, and the importance of cell junction stability. A fitness fingerprint, mediated by flower (hFWE) protein isoforms, dictates that cells expressing the flower-win isoforms will outcompete adjacent flower-loss-expressing cells. The impact of the flower protein isoforms is seen in cancer progression and may have diagnostic potential. The yes-associated protein (YAP) and TAZ transcription factors, central mediators of the oncogenic Hippo pathway, elevate peritumoral fitness thereby protecting against tumor progression and provide a suppressive barrier. Similarly, COL17A1 is a key component in hemidesmosome stability, and its expression in epidermal stem cells contributes to fitness competition and aging characteristics. The contributions of these pathways to disease development and progression will help define how CC is hijacked to favor cancer growth. Understanding these features will also help frame the diagnostic and therapeutic possibilities that may place CC in the crosshairs of cancer therapeutics.

Keywords: COL17A1; TAZ; YAP; aging; cancer; cell competition; cell fitness; cell junction; epidermal stem cells; flower protein; hFWE; hippo pathway; oncogenic pathway; outcompete.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Illustration of cellular competition in cancer and aging skin. First column: hFWE win-expressing tumor cells outcompete adjacent stroma cells expressing hFWE loss. Second column: cells with a loss of YAP/TAZ expression in stroma cells are overtaken by YAP/TAZ abundant tumor cells. Third column: representation of epidermal stem cell competition in the context of COL17A1 expression. Low-COL17A1-expressing epidermal stem cells, which present characteristics of aged skin, are outcompeted by stem cells with higher COL17A1 expression.
See this image and copyright information in PMC

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