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Open AccessArticle

Nodal Facilitates Differentiation of Fibroblasts to Cancer-Associated Fibroblasts that Support Tumor Growth in Melanoma and Colorectal Cancer

1
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
2
Department of Pharmacology, School of Pharmaceutical Sciences, Jinan University, Guangzhou 510632, China
*
Author to whom correspondence should be addressed.
Cells 2019, 8(6), 538; https://doi.org/10.3390/cells8060538
Received: 15 May 2019 / Revised: 2 June 2019 / Accepted: 3 June 2019 / Published: 4 June 2019
(This article belongs to the Special Issue Tumor Microenvironment: Interaction and Metabolism)
Fibroblasts become cancer-associated fibroblasts (CAFs) in the tumor microenvironment after activation by transforming growth factor-β (TGF-β) and are critically involved in cancer progression. However, it is unknown whether the TGF superfamily member Nodal, which is expressed in various tumors but not expressed in normal adult tissue, influences the fibroblast to CAF conversion. Here, we report that Nodal has a positive correlation with α-smooth muscle actin (α-SMA) in clinical melanoma and colorectal cancer (CRC) tissues. We show the Nodal converts normal fibroblasts to CAFs, together with Snail and TGF-β signaling pathway activation in fibroblasts. Activated CAFs promote cancer growth in vitro and tumor-bearing mouse models in vivo. These results demonstrate that intercellular crosstalk between cancer cells and fibroblasts is mediated by Nodal, which controls tumor growth, providing potential targets for the prevention and treatment of tumors. View Full-Text
Keywords: Nodal; CAFs; differentiation; tumor growth; melanoma; colorectal cancer Nodal; CAFs; differentiation; tumor growth; melanoma; colorectal cancer
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MDPI and ACS Style

Li, Z.; Zhang, J.; Zhou, J.; Lu, L.; Wang, H.; Zhang, G.; Wan, G.; Cai, S.; Du, J. Nodal Facilitates Differentiation of Fibroblasts to Cancer-Associated Fibroblasts that Support Tumor Growth in Melanoma and Colorectal Cancer. Cells 2019, 8, 538.

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