Elucidation of Novel mechanisms regulating the tumor suppressor RBL1/p107 levels in mesothelioma and lung cancer cells

The retinoblastoma-like (RBL)1/p107 protein is a member of the retinoblastoma (RB) family including the retinoblastoma (RB)1/p105 protein and RBL2/p130. They are key regulators of the cell cycle and play a central role in modulating cell proliferation. 

RB proteins act as tumor suppressors and their dysregulation is associated with tumor initiation. However, the mechanisms regulating RB protein actions are still very poorly characterized. 

A team of investigators from the Sbarro Institute for Cancer Research and Molecular Medicine, and the Center for Biotechnology at Temple University, including Dr. Elisa Ventura, Dr. Antonio Giordano and Dr. Andrea Morrione, in collaboration with Dr. Francesca Pentimalli and Dr. Carmelina Antonella Iannuzzi from the Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples, Italy, has recently elucidated mechanisms modulating RBL1/p107 levels.

The study entitled “RBL1/p107 Expression Levels Are Modulated by Multiple Signaling Pathways” has been recently accepted in the international-peer-reviewed journal Cancers.

These novel observations demonstrated that, in lung cancer and mesothelioma cells, RBL1/p107 levels and phosphorylation are modulated by a complex network of functional interactions involving Ca2+-dependent signaling (CaMKs), calpain and their ability to directly or indirectly regulate the cell cycle, pointing out a substantial difference with the mechanisms regulating RBL2/p130 stability. 

As stated by Drs. Morrione and Giordano, this work is important to better understand how RB protein levels/activities are modulated and the role that oncogenic pathways play in this process, as in fact the identification of novel regulators of the tumor suppression function of RB proteins might open new strategies for therapy.

About the Sbarro Health Research Organization (SHRO)

The Sbarro Health Research Organization is a non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and related chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism (www.shro.org)