Cancer-associated fibroblasts promote cancer stemness by inducing expression of the chromatin-modifying protein CBX4 in squamous cell carcinoma

Fisher, Matthew L, Balinth, Seamus, Hwangbo, Yon, Wu, Caizhi, Ballon, Carlos, Goldberg, Gary L, Mills, Alea A (August 2023) Cancer-associated fibroblasts promote cancer stemness by inducing expression of the chromatin-modifying protein CBX4 in squamous cell carcinoma. Carcinogenesis, 44 (6). pp. 485-496. ISSN 0143-3334

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Abstract

The chromobox-containing protein CBX4 is an important regulator of epithelial cell proliferation and differentiation, and has been implicated in several cancer types. The cancer stem cell (CSC) population is a key driver of metastasis and recurrence. The undifferentiated, plastic state characteristic of CSCs relies on cues from the microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the microenvironment that can influence the CSC population through the secretion of extracellular matrix and a variety of growth factors. Here we show CBX4 is a critical regulator of the CSC phenotype in squamous cell carcinomas of the skin and hypopharynx. Moreover, CAFs can promote the expression of CBX4 in the CSC population through the secretion of interleukin-6 (IL-6). IL-6 activates JAK/STAT3 signaling to increase ∆Np63α-a key transcription factor that is essential for epithelial stem cell function and the maintenance of proliferative potential that is capable of regulating CBX4. Targeting the JAK/STAT3 axis or CBX4 directly suppresses the aggressive phenotype of CSCs and represents a novel opportunity for therapeutic intervention.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification diseases & disorders > cancer > cancer-associated cell types diseases & disorders > cancer > cancer-associated cell types > cancer-associated fibroblast bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes organs, tissues, organelles, cell types and functions > organs types and functions > metabolism organs, tissues, organelles, cell types and functions > organs types and functions organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:	Fisher, Matthew L Balinth, Seamus Wu, Caizhi Ballon, Carlos Mills, Alea A.
Communities:	CSHL labs > Mills lab CSHL Cancer Center Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL Cancer Center Shared Resources > Antibody and Phage Display Service
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	18 August 2023
Date Deposited:	21 Sep 2023 13:24
Last Modified:	09 Feb 2024 14:26
PMCID:	PMC10436759
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/40931

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