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Targeting an RNA polymerase II-associated PHF5A protein subcomplex with a KMT2A-WDR5 inhibitor impairs self-renewal and tumorigenicity of pancreatic cancer stem cells

ABSTRACT: Pancreatic cancer (PC) remains one of the most aggressive and life-threatening malignancies known for its notorious resistance to chemotherapy. This is increasingly ascribed to the subpopulation of undifferentiated cells, known as pancreatic cancer stem cells (PCSCs), which are evolutionary fitter than other tumor cells to evade the cytotoxic effects of chemotherapy. Those cells are crucial for tumor relapse as they possess ‘stem cell-like’ features of self-renewal and differentiation. However, what molecular mechanisms maintain the unique characteristics of PCSCs are poorly understood. Here, we identified an RNA polymerase II-associated PHF5A-PHF14-HMG20A-RAI1-KMT2A transcriptional subcomplex, which regulates the stemness characteristics and tumorigenicity of PCSCs through epigenetic control of gene expression. Targeting the protein subcomplex with a KMT2A-WDR5 inhibitor attenuated the self-renewal and in vivo tumorigenicity of PCSCs, thus offering a novel anti-PCSCs targeting strategy for enhancing the efficiency of chemotherapy which is likely to translate into durable clinical responses in PC patients.

INSTRUMENT(S): Dionex instrument model

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pancreas

SUBMITTER: Siwei Deng

LAB HEAD: Siim Pauklin

PROVIDER: PXD038378 | Pride | 2023-08-23

REPOSITORIES: Pride

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			Action	DRS
	PEAK_IgG_coIP_ABCG2.L3.6pl_tumoursphere.mgf	Mgf
	PEAK_IgG_coIP_L3.6pl_monolayer_rep1.mgf	Mgf
	PEAK_IgG_coIP_L3.6pl_monolayer_rep2.mgf	Mgf
	PEAK_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep1.mgf	Mgf
	PEAK_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep2.mgf	Mgf

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