A role for CXCR2 in senescence, but what about in cancer?
Senescence is an irreversible arrest triggered by stresses such as telomere shortening, DNA damage, or oncogenic signaling. Oncogene-induced senescence occurs in preneoplastic lesions, but it is absent from full-blown malignancies suggesting a tumor suppressor function. We recently found that depletion of the receptor CXCR2 [which binds to chemokines such as interleukin (IL)-8 or GROalpha] delays both replicative senescence and impairs the senescence response to oncogenic signals. Our findings suggest that signaling by IL-8 and GROalpha might limit tumor growth by reinforcing senescence early in tumorigenesis. The challenge remains in how to integrate this with the well-known tumor promoting effects of IL-8 and GROalpha.
Acosta
Juan C
JC
Cell Proliferation Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, London, United Kingdom.
Gil
Jesús
J
D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D054360:Chemokine CXCL1 / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D015398:Signal Transduction
D054360:Chemokine CXCL1; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B