Cell Competition Boosts Clonal Evolution and Hypoxic Selection in Cancer

Various pathways are involved in cell competition (CC), which tumor cells rely on to acquire a competitive advantage leading to growth and metastasis. Hypoxia is characterized by low oxygen levels; CC and hypoxia have been associated, as the expression of some CC-related genes is influenced by hypoxia-inducible factors and influences cancer outcome. Clonal stem cell selection contributes to tumor heterogeneity since the development of mutations in a fraction of stem cells in a niche can lead to their selection. This heterogeneity contributes to competition, which ultimately affects cancer detection, targeting, and prognosis. CC maintains immune homeostasis, function, and development, which prevents immune malignancies. The comparison of fitness between cells leads to the elimination of less competent cells in the presence of more competent neighbors via cell competition (CC). This phenomenon has been linked with several cancer-related genes and thus may play an important role in cancer. Various processes are involved in the regulation of tumor initiation and growth, including tumor hypoxia, clonal stem cell selection, and immune cell response, all of which have been recently shown to have a potential connection with the mechanisms involved in CC. This review aims to unravel the relation between these processes and competitive cell interactions and how this affects disease progression. The comparison of fitness between cells leads to the elimination of less competent cells in the presence of more competent neighbors via cell competition (CC). This phenomenon has been linked with several cancer-related genes and thus may play an important role in cancer. Various processes are involved in the regulation of tumor initiation and growth, including tumor hypoxia, clonal stem cell selection, and immune cell response, all of which have been recently shown to have a potential connection with the mechanisms involved in CC. This review aims to unravel the relation between these processes and competitive cell interactions and how this affects disease progression. a CC mechanism by which transformed cells are eliminated from the epithelia, allowing ‘loser’ cells to be eliminated while ‘winner’ cells proliferate [78.Ohsawa S. et al.Cell extrusion: a stress-responsive force for good or evil in epithelial homeostasis.Dev. Cell. 2018; 44: 532Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar]. a phenomenon through which epithelial cells lose their polarity and acquire migratory potential, thus promoting metastasis formation. The mechanisms involve the regulation of proteins such as E-cadherin and increase of mesenchymal markers [79.Yang J. et al.Guidelines and definitions for research on epithelial–mesenchymal transition.Nat. Rev. Mol. Cell Biol. 2020; 21: 341-352Crossref PubMed Scopus (249) Google Scholar].