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Spotlighting the hypoxia‐centrosome amplification axis
Author(s) -
Mittal Karuna,
Aneja Ritu
Publication year - 2020
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.21663
Subject(s) - hypoxia (environmental) , centrosome , cancer research , biology , in vivo , cancer cell , in vitro , mitosis , cell culture , tumor hypoxia , cell , microbiology and biotechnology , cancer , cell cycle , medicine , chemistry , genetics , organic chemistry , oxygen , radiation therapy
The abysmal success rate of anticancer drugs in clinical trials, is in part, attributable to discordance between cultured cancer cells and patient tumors. While tumors in vivo, display a lower mitotic index, patient tumors portray much higher centrosomal aberrations, relative to in vitro cultured cells. The microenvironment too differs considerably between the in vitro and in vivo scenarios. Notably, another hallmark of cancer, hypoxia, is not recapitulated in cell lines cultured under normoxic conditions. These observations raise the possibility that hypoxia may be the missing link that explains the discordance between cell biological phenomena in vitro versus physiological conditions. Further, the interplay between hypoxia and centrosome amplification (CA) is relatively understudied. Recent research from our laboratory, geared toward examining the biological link between the two, has uncovered that hypoxia induces the expression of proteins (Plk4, Aurora A, Cyclin D) implicated in CA, in a hypoxia‐inducible factor 1α (HIF‐1α)‐dependent context. Our studies evidence that hypoxia fuels CA that underlie intratumoral heterogeneity and metastatic potential of cancer cells. Given the advent of HIF‐1α inhibitors, this research has ramifications in aiding patient risk stratification and designing new cancer drug therapies to facilitate clinical decision‐making.