Grant: Project Grant

Receptors located at the surface of the cell integrate the extracellular environment towards cellular functions such as cell survival, proliferation and migration. To efficiently control extracellular signals, cell surface receptor levels and turnover is tightly regulated. This process is orchestrated by the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery, composed of several cellular proteins. Importantly, ESCRT components are essential for the attenuation of the cell surface signalling. Impairment in ESCRT function leads to receptor stabilization, persistent signalling, and cancer promotion. During cancer progression, some genes that prevent tumor development are inactivated and are called tumor suppressors. The identification and characterization of these tumor suppressors is essential to develop new cancer therapies. Our previous work identified HD-PTP, a new member of the ESCRT complex, as a novel tumor suppressor. Indeed, inactivation of HD-PTP in mice leads to development of lung cancer and lymphoma. Interestingly, we have shown that UBAP1 and Endofin, two novel ESCRT components and HD-PTP binding partners, share HD-PTP functions. Therefore, we hypothesize that HD-PTP and its binding partners (UBAP1 and Endofin) exert tumor suppressor functions. This research project aims to characterize the physiological function of HD-PTP/UBAP1/Endofin-containing novel ESCRT complex and to determine their role in tumor development. Moreover, since ESCRTs play a central role in a wide range of signaling pathways activated downstream of numerous cell surface receptors this project might have significant implications in the development of new therapeutic strategies that would be applicable to a wide range of cancers.