Decreased expression of the type III TGF-β receptor enhances metastasis and invasion in hepatocellullar carcinoma progression

Zhang,Sen; Sun,Wu-Yi; Wu,Jing-Jing; Gu,Yuan-Jing; Wei,Wei

doi:10.3892/or.2016.4615

Decreased expression of the type III TGF-β receptor enhances metastasis and invasion in hepatocellullar carcinoma progression

Authors:
- Sen Zhang
- Wu-Yi Sun
- Jing-Jing Wu
- Yuan-Jing Gu
- Wei Wei
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Affiliations: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti‑inflammatory and Immune Medicine of the Chinese Education Ministry, Anhui Collaborative Innovation Center of Anti‑inflammatory and Immune Medicine, Hefei, Anhui 230032, P.R. China
Published online on: February 8, 2016 https://doi.org/10.3892/or.2016.4615
Pages: 2373-2381

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Abstract

The transforming growth factor β (TGF-β) superfamily of cytokines is multifunctional and involved in the regulation of cell growth and differentiation. TGF-β can induce an epithelial-mesenchymal transition (EMT) of both epithelial and endothelial cells. This has consequences for cancer progression in regards to both migration and invasion abilities. The type III TGF-β receptor (TβRIII) is a ubiquitously expressed TGF-β co-receptor which regulates TGF-β signaling and the progression of various types of cancer. Previous studies have shown that TβRIII exhibits abnormal expression and plays an essential role in regulating cancer invasion and metastasis, while little is known in regards to its role in hepatocellular carcinoma (HCC) progression. In the present study, we designed the present research to study the role of TβRIII in the invasion and metastasis of HCC and the possible mechanisms involved. The results demonstrated decreased expression of TβRIII in HCC patient tissues and human HCC cell lines. TGF-β1 stimulation led to the increased migratory ability and reduced expression of TβRIII in HCC cells. In addition, knockdown of TβRIII by small interfering RNA (siRNA) promoted the migration and invasion of HCC cells and induced activation of the Smad2 and Akt pathways. All the results suggest that TβRIII is a novel suppressor of HCC progression.

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