AUTHOR=Boudhraa Zied , Carmona Euridice , Provencher Diane , Mes-Masson Anne-Marie TITLE=Ran GTPase: A Key Player in Tumor Progression and Metastasis JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=Volume 8 - 2020 YEAR=2020 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00345 DOI=10.3389/fcell.2020.00345 ISSN=2296-634X ABSTRACT=

Ran (Ras-related nuclear protein) GTPase is a member of the Ras superfamily. Like all the GTPases, Ran cycles between an active (GTP-bound) and inactive (GDP-bound) state. However, Ran lacks the CAAX motif at its C-terminus, a feature of other small GTPases that ensures a plasma membrane localization, and largely traffics between the nucleus and the cytoplasm. Ran regulates nucleo-cytoplasmic transport of molecules through the nuclear pore complex and controls cell cycle progression through the regulation of microtubule polymerization and mitotic spindle formation. The disruption of Ran expression has been linked to cancer at different levels – from cancer initiation to metastasis. In the present review, we discuss the contribution of Ran in the acquisition of three hallmarks of cancer, namely, proliferative signaling, resistance to apoptosis, and invasion/metastasis, and highlight its prognostic value in cancer patients. In addition, we discuss the use of this GTPase as a therapeutic target in cancer.