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Survivin belongs to the inhibitors of apoptosis (IAPs) protein family which plays diverse roles in cell division, cell death inhibition, as well as DNA repair. Elevated survivin expression is found in most cancers and often indicates greater cancer aggression and poor prognostic outcome for patients. Survivin expression is also associated with resistance to chemo- and radiotherapy, and is implicated in an increased likelihood for cancer relapse.
A recent study by Wang et al. (2019) describes a new link between survivin and the ability of prostate cancer cells to elude killing by radiation therapy. The researchers discovered that the oncoprotein αvβ3 integrin, a cell surface receptor with signaling pathways associated with cancer pathogenesis, promotes radio-resistance by regulating survivin levels. Specifically, they found that αvβ3 integrin increased cell survival and prevented the downregulation of survivin expression in prostate cancer cells after exposure to ionizing radiation. They went on to show that decreasing survivin expression in αvβ3 integrin-expressing prostate cancer cells sensitized the cells to radiation and decreased cell growth and survival. They additionally showed that overexpressing survivin in these cells was able to rescue growth and survival after exposure to radiation.
Survivin has long been an attractive target for cancer treatment because its expression is absent in fully differentiated adult tissue but upregulated in cancer cells. Promising immunotherapeutic strategies targeting survivin are in development, including SurVaxM, a cancer vaccine currently in clinical trials. Anti-survivin monoclonal antibodies were also found to have an antitumor effect and even increase the lifespan of mice across various murine tumor models (Fenstermaker, 2018). While more research is certainly needed to better elucidate the connection between integrin signaling and survivin expression, this study adds a new dimension to survivin’s already complex signaling networks and highlights new opportunities for therapy development.
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