P62 sustains a protumorigenic gene signature in melanoma opposing mRNA-dependent decay
Ontology highlight
ABSTRACT:
INSTRUMENT(S): maXis
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cell Culture
SUBMITTER: 
Nuria Ibarz
LAB HEAD: Javier Muñoz
PROVIDER: PXD007000 | Pride | 2021-10-29
REPOSITORIES: Pride
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Project description:Metastasis is a common cancer hallmark which however, may be acquired by tumor-type specific mechanisms. Here we identify p62/SQSTM1 as a modulator of metastatic genes selectively enriched in melanoma. Loss- and gain-of-function analyses of p62 effectors revealed FERMT2 as an indicator of poor patient prognosis. Analyses in tumor cells, clinical biopsies and genetically-engineered mice (to compare p62 vs. ATG5) demonstrated that known p62 roles in autophagy and stress responses were not essential in melanomas. Instead, a genome-wide transcriptomic/proteomic/interactomic approach demonstrated that p62 controls FERMT2 and yet additional pro-metastatic genes by modulating transcript stability. This function of p62 was exerted by recruiting RNA-binding proteins, here exemplified by IGF2BP1. These data illustrate how genetically altered cancers can coordinately fuel pro-metastatic signatures.
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Project description:Metastasis is a common cancer hallmark which however, may be acquired by tumor-type specific mechanisms. Here we identify p62/SQSTM1 as a modulator of metastatic genes selectively enriched in melanoma. Loss- and gain-of-function analyses of p62 effectors revealed FERMT2 as an indicator of poor patient prognosis. Analyses in tumor cells, clinical biopsies and genetically-engineered mice (to compare p62 vs. ATG5) demonstrated that known p62 roles in autophagy and stress responses were not essential in melanomas. Instead, a genome-wide transcriptomic/proteomic/interactomic approach demonstrated that p62 controls FERMT2 and yet additional pro-metastatic genes by modulating transcript stability. This function of p62 was exerted by recruiting RNA-binding proteins, here exemplified by IGF2BP1. These data illustrate how genetically altered cancers can coordinately fuel pro-metastatic signatures.
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