Hippo Pathway Regulation and Microenvironmental Cues Governing Human MSC Transition to Cancer-Associated Fibroblasts

IF 4 2区生物学 Q2 CELL BIOLOGY

Journal of Cellular Physiology Pub Date : 2026-08-05 DOI:10.1002/jcp.70219

Pimjai Chingsuwanrote, Chanchao Lorthongpanich, Pakpoom Kheolamai, Ting Gang Chew, Chuti Laowtammathron, Sudjit Luanpitpong, Rangsun Parnpai, Surapol Issaragrisil

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引用次数: 0

Abstract

Cancer-associated fibroblasts (CAFs) are key drivers of tumor progression. This study examined how three-dimensional (3D) culture, hypoxia, and cancer-derived soluble factors influence the transformation of human mesenchymal stem cells (hMSCs) into inflammatory CAFs (iCAFs). hMSCs from bone marrow, placenta, and chorion were cultured in 2D, in Matrigel-based 3D systems, under hypoxia, and with soluble factors from colon cancer cells (HT29, HCT116). 3D culture strongly induced iCAF markers (IL1α, CSF3, IL6) while reducing myofibroblastic CAF markers (CCN2, MYL9, TAGLN). Hypoxia and cancer factors further enhanced this phenotype, promoting IL1α/IL6 secretion and shifting their influence from suppressing to stimulating cancer cell growth and angiogenesis. Mechanistically, these changes were associated with YAP/TAZ down-regulation, and genetic depletion of YAP/TAZ alone was sufficient to convert hMSCs into iCAFs even in 2D culture. These findings highlight YAP/TAZ as critical regulators of hMSC-to-CAF transformation, with implications for therapeutic strategies targeting tumor stroma.

查看原文本刊更多论文

Hippo通路调控和微环境信号调控人间充质干细胞向癌症相关成纤维细胞的转变。

癌症相关成纤维细胞（CAFs）是肿瘤进展的关键驱动因素。本研究考察了三维（3D）培养、缺氧和癌源性可溶性因子如何影响人间充质干细胞（hMSCs）向炎性CAFs （iCAFs）的转化。来自骨髓、胎盘和绒毛膜的hMSCs分别在2D、基于matrigel的3D系统中、缺氧条件下与结肠癌细胞的可溶性因子一起培养（HT29, HCT116）。3D培养强烈诱导iCAF标记（IL1α, CSF3, IL6），同时降低肌成纤维细胞CAF标记（CCN2, MYL9， TAGLN）。缺氧和癌症因素进一步增强了这种表型，促进了IL1α/IL6的分泌，并将其影响从抑制癌细胞生长和血管生成转变为刺激。从机制上讲，这些变化与YAP/TAZ下调有关，即使在2D培养中，仅YAP/TAZ基因缺失也足以将hMSCs转化为icaf。这些发现强调了YAP/TAZ是hmsc向caf转化的关键调节因子，对靶向肿瘤基质的治疗策略具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cellular Physiology 生物-生理学

CiteScore

14.70

自引率

0.00%

发文量

256

审稿时长

1 months

期刊介绍： The Journal of Cellular Physiology publishes reports of high biological significance in areas of eukaryotic cell biology and physiology, focusing on those articles that adopt a molecular mechanistic approach to investigate cell structure and function. There is appreciation for the application of cellular, biochemical, molecular and in vivo genetic approaches, as well as the power of genomics, proteomics, bioinformatics and systems biology. In particular, the Journal encourages submission of high-interest papers investigating the genetic and epigenetic regulation of proliferation and phenotype as well as cell fate and lineage commitment by growth factors, cytokines and their cognate receptors and signal transduction pathways that influence the expression, integration and activities of these physiological mediators. Similarly, the Journal encourages submission of manuscripts exploring the regulation of growth and differentiation by cell adhesion molecules in addition to the interplay between these processes and those induced by growth factors and cytokines. Studies on the genes and processes that regulate cell cycle progression and phase transition in eukaryotic cells, and the mechanisms that determine whether cells enter quiescence, proliferate or undergo apoptosis are also welcomed. Submission of papers that address contributions of the extracellular matrix to cellular phenotypes and physiological control as well as regulatory mechanisms governing fertilization, embryogenesis, gametogenesis, cell fate, lineage commitment, differentiation, development and dynamic parameters of cell motility are encouraged. Finally, the investigation of stem cells and changes that differentiate cancer cells from normal cells including studies on the properties and functions of oncogenes and tumor suppressor genes will remain as one of the major interests of the Journal.