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

ABSTRACT: Pancreatic cancer remains one of the most aggressive and lethal cancers in humans. It is undeniably known for its notorious resistance to conventional chemotherapeutics which are often associated with a transient response to treatment but rapidly followed by drug resistance and tumor recurrence. Increasing evidence suggests that therapy failure in pancreatic cancer is largely ascribed to the residual subpopulation of undifferentiated cells, known as cancer stem cells (CSCs), which are evolutionary 'fitter' than other tumor cells to evade the cytotoxic effects of chemotherapy. Those cells are outstandingly critical for tumor relapse as they possess unique 'stem cell-like' features of self-renewal and differentiation which render them capable of regenerating the original tumor. Through the identification of key epigenetic regulators of CSCs phenotypes and functions, this project seeks to gain insight into the molecular mechanisms underlying tumor recurrence and identify novel therapeutic candidates for eliminating CSCs and achieving long-term clinical responses in pancreatic cancer patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217329 | GEO | 2023/08/10

REPOSITORIES: GEO

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

Project description:Pancreatic cancer remains one of the most aggressive and lethal cancers in humans. It is undeniably known for its notorious resistance to conventional chemotherapeutics which are often associated with a transient response to treatment but rapidly followed by drug resistance and tumor recurrence. Increasing evidence suggests that therapy failure in pancreatic cancer is largely ascribed to the residual subpopulation of undifferentiated cells, known as cancer stem cells (CSCs), which are evolutionary 'fitter' than other tumor cells to evade the cytotoxic effects of chemotherapy. Those cells are outstandingly critical for tumor relapse as they possess unique 'stem cell-like' features of self-renewal and differentiation which render them capable of regenerating the original tumor. Through the identification of key epigenetic regulators of CSCs phenotypes and functions, this project seeks to gain insight into the molecular mechanisms underlying tumor recurrence and identify novel therapeutic candidates for eliminating CSCs and achieving long-term clinical responses in pancreatic cancer patients.

2023-08-10 | GSE217331 | GEO

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

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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

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Abernathy2016 - glioblastoma treatment

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2023-03-11 | PXD037275 | Pride

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Expression data from LNCaP cells

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Project description:The prognosis of pancreatic cancer is still poor due to resistance to conventional therapies, and cancer stem cells (CSCs) targeted therapy is expected to be a promising therapy. Although epithelial mesenchymal transition-inducing transcription factors (EMT-TF) are known to impart the CSCs properties to some of solid tumors, it has not been clearly reported in pancreatic cancer yet. Zinc finger protein SNAI2, a member of the Snail superfamily of EMT-TF, is frequently overexpressed in pancreatic cancer cells and the poor prognosis has been reported in cases with high SNAI2 expression. we found the suppression of SNAI2 expression using RNA interference decreased the tumorigenicity in the tumor spheroid (Sph) derived from surgically resected pancreatic cancer tissues. Also, it increased the sensitivities to Gemcitabine treatment and reduced the expression of CD44, one of the pancreatic CSCs markers. Furthemore, microarray analysis suggests that the mechanism is mediated by insulin-like growth factor binding protein 2 (IGFBP2). These results indicate that SNAI2 may be a critical factor for the CSCs properties and indispensable for the homeostasis of pancreatic CSCs.

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