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SUMOylation regulates nucleo-cytoplasmic shuttling of LKB1 in liver cancer

ABSTRACT: Even though liver kinase B1 (LKB1) is commonly described as a tumor suppressor, we and others have shown that LKB1 is augmented in liver cancer. In agreement, LKB1 modulation in human hepatoma cells and mouse livers induces changes in cell proliferation and the appearance of liver neoplastic lesions in association with disruptions of energetic metabolism. After LKB1 overexpression, a surprising uncoupling between LKB1 and its downstream kinase AMP-activated protein kinase is observed as well as activation of the oncogenic Ras pathway, driven by the direct or indirect binding of LKB1 to the promoter region of the Ras activator, RASGRP3. Under these circumstances, LKB1 SUMOylation at Lys178 by SUMO-2, the main SUMO paralogue present in liver, promotes LKB1 nuclear localization, fueling hepatoma cell proliferation. Overall, SUMO-2 mediated modification of LKB1 at Lys178 is suggested as a bona fide oncogenic driver in liver cancer by regulating the nucleo-cytoplasmic shuttling of LKB1.

ORGANISM(S): Mus musculus

PROVIDER: GSE99584 | GEO | 2018/09/11

REPOSITORIES: GEO

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