Mutant p53 Drives Cancer Metastasis via RCP-Mediated Hsp90α Secretion
Shaosen Zhang, Caihong Wang, Boyuan Ma, Min Xu, Siran Xu, Jie Liu, Yang Tian, Yan Fu, Yongzhang Luo
Abstract
mice and attenuates the invasiveness of p53 mutant tumors. Furthermore, mass spectrometry and functional analysis identified a critical role for Rab coupling protein (RCP) in mutp53-induced Hsp90α secretion. RCP knockdown decreases eHsp90α levels and inhibits malignant progression. Notably, recombinant Hsp90α re-introduction markedly rescues the impaired migration and invasion abilities caused by RCP depletion. Taken together, these findings elucidate the molecular mechanisms by which mutp53 executes oncogenic activities via its downstream RCP-mediated Hsp90α secretion and a strategy to treat human cancers expressing mutp53 proteins.
Topics & Concepts
SecretionBiologyHeat shock proteinHsp90MutantGene knockdownExosomeCancer researchWild typeCell biologyMicrovesiclesEndocrinologymicroRNAApoptosisBiochemistryGeneHeat shock proteins researchEndoplasmic Reticulum Stress and DiseaseEnzyme Structure and Function