RIP1, a novel oncogenic driver in melanoma

 

Most previous studies have demonstrated a key role for RIP1, a receptor-binding protein kinase, in activating cell death signaling. However, it has been reported that RIP1^-/- mice develop extensive apoptosis in many selected tissues and early death, indicating that RIP1 may function in cell survival in specific types of tissues. Liu et al. found that RIP1 plays a role as an oncogenic driver in human melanoma. The article was published in Cancer Research.

 

Researchers found RIP1 silencing inhibited melanoma development both in vitro and in vivo. Although RIP1 overexpression induced apoptosis in a small proportion of melanoma cells, it promotes proliferation in the rest of cells via NF-κB pathway. Mechanically, ectopic expression of RIP1 triggered anchorage-independent cell growth of primary melanocytes in a NF-κB-dependent manner. Two mechanisms involve in the upregulation of RIP1 in human melanomas: gain of DNA copy number and constitutive ubiquitination by a TNFα autocrine loop. Together, the findings reveal function of RIP1 as a oncogenic driver dependents on NF-κB signaling, and may work as a potential therapeutic target to treat melanoma.

 

Reference:
Cancer Res. 2015 Feb 27. pii: canres.2199.2014.

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