Temporal proteomic analysis unravels the hypoxic response of melanoma cells

ABSTRACT: Hypoxia is a common feature in various solid tumors including melanoma. Cancer cells in hypoxic environments are resistant to both chemotherapy and radiation. Hypoxia is also associated with immune suppression. Identification of proteins and pathways that regulate survival of cancer cells in hypoxic environments can reveal potential vulnerabilities that can be exploited to improve efficacy of anti-cancer therapy. We carried out global proteome and phosphoproteome profiling in melanoma cell lines to identify proteins and pathways that are induced by hypoxia. Here, using Orbitrap Fusion Mass Spectrometer for analysis and employing TMT-based quantitation, we report >7,000 proteins and >10,000 phosphosites. As expected, several proteins that are known targets of hypoxia inducible factors (HIFs) were found to be overexpressed in the hypoxic models. In addition, several metabolic enzymes showed altered expression revealing metabolic reprogramming in hypoxic conditions. Phosphoproteomic profiling revealed kinase mediated signaling pathways that are induced in hypoxic conditions. Our data provides a comprehensive view of proteomic and phosphoproteomic alterations in hypoxia and reveals potential mechanisms that regulate cell survival in hypoxic environments. These mechanisms can be targeted to improve therapeutic outcomes in cancer treatment. Further, we identify the 20S proteasome as a putative therapeutic target in melanoma.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Melanocyte, Cell Culture

SUBMITTER: Harsha Gowda  

LAB HEAD: Harsha Gowda

PROVIDER: PXD019832 | Pride | 2021-05-31

REPOSITORIES: Pride