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MELK promotes melanoma growth by stimulating the NF-B pathway

ABSTRACT: Melanoma accounts for over 80% of skin cancer-related deaths and current therapies provide only short-term benefit to patients. Here, we show in melanoma cells that maternal embryonic leucine zipper kinase (MELK) is transcriptionally upregulated by the MAP kinase pathway via transcription factor E2F1. MELK knockdown or pharmacological inhibition blocked melanoma growth and enhanced the effectiveness of BRAFV600E inhibitor against melanoma cells. To identify mediators of MELK function, we performed stable isotope labeling with amino acids in cell culture (SILAC) and identified 469 proteins that had downregulated phosphorylation after MELK inhibition. Remarkably, 139 of these proteins were previously reported as substrates of BRAF or MEK, demonstrating that MELK is an important downstream mediator of the MAPK pathway. Furthermore, we show that MELK promotes melanoma growth by activating NF-B pathway activity via Sequestosome 1 (SQSTM1/p62). Collectively, these results underpin an important role for MELK in melanoma growth, downstream of the MAPK pathway.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: narendra wajapeyee

LAB HEAD: Narendra Wajapayee

PROVIDER: PXD007872 | Pride | 2017-12-07

REPOSITORIES: Pride

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			Action	DRS
	OTF16-311.raw	Raw
	OTF16-788.raw	Raw
	Rado_SILAC_375_Elution.pep.xml	Pepxml
	Rado_SILAC_M14-Elution.pep.xml	Pepxml

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