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Cell State Dependent Effects of Bmal1 on Melanoma Immunity and Tumorigenicity

ABSTRACT: The circadian clock regulator Bmal1 modulates tumorigenesis, but its reported effects are often inconsistent. Here, we show that Bmal1 has a context-dependent role in mouse melanoma tumor growth. Loss of Bmal1 in YUMM or B16 melanoma cells eliminated clock function, and diminished hypoxic gene expression signature and tumorigenesis, which could be rescued by ectopic expression of HIF-1a. By contrast, over-expressed wild-type or a dominant negative Bmal1 non-canonically sequestered myosin heavy chain 9 (Myh9) to increase MRTF-SRF activity and AP-1 transcriptional signature, and shift YUMM 2.1 cells from a Sox10high to a Sox9high immune resistant, mesenchymal cell state that is found in human melanomas. Our work uncovers a link between Bmal1, Myh9, mouse melanoma cell plasticity, and tumor immunity. This connection may underlie cancer therapeutic resistance and underpin the link between the circadian clock, MRTF-SRF and the cytoskeleton.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Chi V. Dang

PROVIDER: MSV000090431 | MassIVE |

SECONDARY ACCESSION(S): PXD037077

REPOSITORIES: MassIVE

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