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How do fibroblasts contribute to tumor suppression through TGF-beta secretion?

Epithelial–mesenchymal transition

Colorectal cancer

Hepatocyte growth factor

Immune checkpoint

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Fibroblasts play a crucial role in tumor suppression through TGF-β secretion. Specifically, TGF-β signaling in fibroblasts has been shown to suppress tumor metastasis by antagonizing HGF/c-Met signaling within tumor epithelial cells. Additionally, cancer-associated fibroblasts (CAFs) secrete TGF-β, which downregulates the expression of Fibronectin leucine-rich transmembrane protein 3 (FLRT3) through activating SMAD4, promoting aggressive phenotypes in colorectal cancer cells. This mechanism highlights how fibroblasts, particularly CAFs, contribute to tumor suppression by modulating the TGF-β/SMAD4 signaling pathway to inhibit tumor progression and metastasis. Targeting this pathway, such as with LY2109761, shows promise as a potential treatment strategy for advanced colorectal cancer.

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Journal Article•DOI TGF-β-induced FLRT3 attenuation is essential for cancer-associated fibroblast-mediated epithelial-mesenchymal transition in colorectal cancer. Mengdi Yang, Dan Li, Zhiyuan Jiang, Changcan Li, Suyuan Ji, Jing Sun, Yu-Lan Chang, Shunyi Ruan, Zhiyu Wang, Rui Liang, Xueyu Dai, Bin Li, Huajun Zhao - Show less +12 more 13 May 2022-Molecular Cancer Research 6 Citations	Fibroblasts promote tumor progression by secreting TGF-β, which downregulates FLRT3 via SMAD4 activation, inducing EMT in colorectal cancer cells. Inhibiting TGF-β signaling shows promise for CRC treatment.
Open access•Journal Article•DOI TGF-β Mediated Immune Evasion in Cancer-Spotlight on Cancer-Associated Fibroblasts. Parisa Ghahremanifard, Ayan Chanda, Shirin Bonni, Pinaki Bose - Show less +3 more 05 Dec 2020-Cancers 33 Citations	Fibroblasts, particularly cancer-associated fibroblasts (CAFs), promote tumor immune evasion by secreting extracellular matrix components under TGF-β influence, creating an immunosuppressive microenvironment in cancer.
Journal Article•DOI TGF-β-Induced FLRT3 Attenuation Is Essential for Cancer-Associated Fibroblast–Mediated Epithelial–Mesenchymal Transition in Colorectal Cancer 13 May 2022-Molecular Cancer Research 7 Citations	Fibroblasts promote tumor progression by secreting TGF-β, which downregulates FLRT3 via SMAD4 activation, inducing EMT in colorectal cancer cells. This process can be targeted for therapeutic intervention.
Posted Content•DOI Data from Enhanced Hepatocyte Growth Factor Signaling by Type II Transforming Growth Factor-β Receptor Knockout Fibroblasts Promotes Mammary Tumorigenesis de Rezende, Guilherme Rocha 30 Mar 2023	Fibroblasts suppress tumor metastasis by inhibiting HGF/c-Met signaling in tumor cells through TGF-β secretion, as shown in the study using Tgfbr2 knockout fibroblasts in a co-xenograft model.
Posted Content•DOI Data from Enhanced Hepatocyte Growth Factor Signaling by Type II Transforming Growth Factor-β Receptor Knockout Fibroblasts Promotes Mammary Tumorigenesis Joan S. M. Meyers 30 Mar 2023	Fibroblasts with intact TGF-β signaling suppress tumor metastasis by inhibiting HGF/c-Met signaling in tumor cells, highlighting a stromal role in tumor suppression through TGF-β modulation.

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