Hic-5 regulates extracellular matrix-associated gene expression and cytokine secretion in cancer associated fibroblasts.

Autor: Xu W; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Goreczny GJ; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY, USA; Jnana Therapeutics, Boston, MA, USA., Forsythe I; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY, USA; Zymo Research Corp, Huntington Beach, CA, USA., Brennan G; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY, USA., Stowell T; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY, USA., Brock K; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY, USA., Capella B; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY, USA., Turner CE; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY, USA. Electronic address: turnerce@upstate.edu.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2024 Feb 15; Vol. 435 (2), pp. 113930. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1016/j.yexcr.2024.113930
Abstrakt: The focal adhesion protein, Hic-5 plays a key role in promoting extracellular matrix deposition and remodeling by cancer associated fibroblasts within the tumor stroma to promote breast tumor cell invasion. However, whether stromal matrix gene expression is regulated by Hic-5 is still unknown. Utilizing a constitutive Hic-5 knockout, Mouse Mammary Tumor Virus-Polyoma Middle T-Antigen spontaneous breast tumor mouse model, bulk RNAseq analysis was performed on cancer associated fibroblasts isolated from Hic-5 knockout mammary tumors. Functional network analysis highlighted a key role for Hic-5 in extracellular matrix organization, with both structural matrix genes, as well as matrix remodeling genes being differentially expressed in relation to Hic-5 expression. The subcellular distribution of the MRTF-A transcription factor and expression of a subset of MRTF-A responsive genes was also impacted by Hic-5 expression. Additionally, cytokine array analysis of conditioned media from the Hic-5 and Hic-5 knockout cancer associated fibroblasts revealed that Hic-5 is important for the secretion of several key factors that are associated with matrix remodeling, angiogenesis and immune evasion. Together, these data provide further evidence of a central role for Hic-5 expression in cancer associated fibroblasts in regulating the composition and organization of the tumor stroma microenvironment to promote breast tumor progression.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: