Proteomics

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E3 ubiquitin ligase HECTD2 mediates melanoma progression and immune evasion


ABSTRACT: The ubiquitin-proteasome system maintains protein homeostasis, underpins the cell cycle and is dysregulated in cancer. However, the role of individual E3 ubiquitin ligases, which mediate the final step in ubiquitin-mediated proteolysis, remains incompletely understood. Identified through screening for cancer-specific endogenous retroviral transcripts, we show that the little studied E3 ubiquitin ligase HECTD2 exerts dominant control of tumour progression in melanoma. HECTD2 cell-autonomously drives the proliferation of human and murine melanoma cells by accelerating the cell cycle. HECTD2 additionally regulates cancer cell production of immune mediators, initiating multiple immune suppressive pathways, which include the cyclooxygenase 2 (COX2) pathway. Accordingly, higher HECTD2 expression is associated with weaker anti-tumour immunity and unfavourable outcome of PD-1 blockade in human melanoma, and counteracts immunity against a model tumour antigen in murine melanoma. This central, multifaceted role of HECTD2 in cancer cell-autonomous proliferation and in immune evasion may provide a single target for a multipronged therapy of melanoma.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Melanocyte

DISEASE(S): Skin Melanoma

SUBMITTER: Joanna Kirkpatrick  

LAB HEAD: George Kassiotis

PROVIDER: PXD025237 | Pride | 2021-07-23

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20210305_CF2188_Clone_DIA_1.raw Raw
20210305_CF2188_Clone_DIA_2.raw Raw
20210305_CF2188_Clone_DIA_3.raw Raw
20210305_CF2188_Clone_DIA_4.raw Raw
20210305_CF2188_Clone_DIA_5.raw Raw
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