RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy
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Paola Indovina1,2, Francesca Pentimalli3, Nadia Casini2, Immacolata Vocca3, Antonio Giordano1,2
1Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA
2Department of Medicine, Surgery and Neuroscience, University of Siena and Istituto Toscano Tumori (ITT), Siena, Italy
3Oncology Research Center of Mercogliano (CROM), Istituto Nazionale Tumori “Fodazione G. Pascale” – IRCCS, Naples, Italy
Antonio Giordano, e-mail: [email protected]
Keywords: RB family, apoptosis, E2F, cancer therapy, CDK inhibitors
Received: May 14, 2015 Accepted: June 06, 2015 Published: June 18, 2015
Inactivation of the retinoblastoma (RB1) tumor suppressor is one of the most frequent and early recognized molecular hallmarks of cancer. RB1, although mainly studied for its role in the regulation of cell cycle, emerged as a key regulator of many biological processes. Among these, RB1 has been implicated in the regulation of apoptosis, the alteration of which underlies both cancer development and resistance to therapy. RB1 role in apoptosis, however, is still controversial because, depending on the context, the apoptotic cues, and its own status, RB1 can act either by inhibiting or promoting apoptosis. Moreover, the mechanisms whereby RB1 controls both proliferation and apoptosis in a coordinated manner are only now beginning to be unraveled. Here, by reviewing the main studies assessing the effect of RB1 status and modulation on these processes, we provide an overview of the possible underlying molecular mechanisms whereby RB1, and its family members, dictate cell fate in various contexts. We also describe the current antitumoral strategies aimed at the use of RB1 as predictive, prognostic and therapeutic target in cancer. A thorough understanding of RB1 function in controlling cell fate determination is crucial for a successful translation of RB1 status assessment in the clinical setting.
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