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Review
. 2017 Aug 7:7:39.
doi: 10.1186/s13578-017-0168-0. eCollection 2017.

TGF-β in pancreatic cancer initiation and progression: two sides of the same coin

Wei Shen #  1 , Guo-Qing Tao #  1 , Yu Zhang  1 , Bing Cai  1 , Jian Sun  1 , Zhi-Qiang Tian  1
Affiliations
Review

TGF-β in pancreatic cancer initiation and progression: two sides of the same coin

Wei Shen et al. Cell Biosci. .

Abstract

Pancreatic cancer is highly lethal malignant tumor with characterised rapid progression, invasiveness and resistance to radiochemotherapy. Transforming growth factor-β (TGF-β) signaling plays a dual role in both pro-tumorigenic and tumor suppressive of pancreatic cancer, depending on tumor stage and microenvironment. TGF-β signaling components alteration are common in pancreatic cancer, and its leading role in tumor formation and metastases has received increased attention. Many therapies have investigated to target TGF-β signaling in the preclinical and clinical setting. In this review, we highlight the dual roles of TGF-β and touch upon the perspectives on therapeutic target of TGF-β signaling in pancreatic cancer.

Keywords: Pancreatic cancer; Transforming growth factor-β; Tumor microenvironment.

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Figures

Fig. 1
Fig. 1
Overview of the TGF-β signaling pathway. TGF-β signaling is transduced through two pathways of Smad (canonical) and non-Smad (non-canonical). In Smad pathway, cell surface complexes of TGFβRI and TGFβRII phosphorylate upon TGF-β ligand binding and activate Smad2 and Smad3. Smad4 and activated Smad2/Smad3 form a Smads complex, and then interacts with other transcription factors to regulate transcription of target genes. TGF-β signaling also activates non-Smad pathways, including PI3K-Akt, Ras-Erk, p38, JNK, and GTPases
Fig. 2
Fig. 2
The dual role of TGF-β in pancreatic cancer cell. (Left) TGFβ-mediated epithelial–mesenchymal transition (EMT) and apoptosis in Smad4-positive pancreatic cancer cell. TGF-β signaling induces EMT by induction SNAIL and repression KLF5. Alternatively, TGF-β signaling induces apoptosis in KLF5 absence cell by SOX4 inducing transcription of pro-apoptotic genes. (Right) TGF-β promotes tumor progression in Smad4-negative pancreatic cancer cell. TGF-β signaling induces SOX4 induction mediated through Smad2/3, and then SOX4 and KLF5 cooperate for tumorigenesis
See this image and copyright information in PMC

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