The Molecular Functions of RalBP1 in Lung Cancer

초록

RalBP1 is an ATP-dependent non-ABC transporter, responsible for the major transport function in many cellsincluding many cancer cell lines, causing efflux of glutathione-electrophile conjugates of both endogenous metabolitesand environmental toxins. RalBP1 is expressed in most human tissues, and is over-expressed in non-small cell lungcancer cell lines and in many other tumor types. Blockade of RalBP1 by various approaches has been shown to increasesensitivity to radiation and chemotherapeutic drugs, leading to cell apoptosis. In xenograft tumor models in mice, RalBP1blockade or depletion results in complete and sustained regression across many cancer cell types including lung cancercells. In addition to its transport function, RalBP1 has many other cellular and physiological functions, based on itsdomain structure which includes a unique Ral-binding domain and a RhoGAP catalytic domain, as well as docking sitesfor multiple signaling proteins. Additionally, RalBP1 is also important for stromal cell function in tumors, as it was recentlyshown to be required for efficient endothelial cell function and angiogenesis in solid tumors. In this review, we discussthe cellular and physiological functions of RalBP1 in normal and lung cancer cells.

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