Transcriptional Induction of Periostin by a Sulfatase 2-TGFβ1-SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma - Université de Rennes Access content directly
Journal Articles Cancer Research Year : 2017

Transcriptional Induction of Periostin by a Sulfatase 2-TGFβ1-SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma

Gang Chen
  • Function : Author
Ikuo Nakamura
  • Function : Author
Renumathy Dhanasekaran
  • Function : Author
Eriko Iguchi
  • Function : Author
Paola A. Romecin
  • Function : Author
Renzo E. Vera
  • Function : Author
Luciana L. Almada
  • Function : Author
Ezequiel J. Tolosa
  • Function : Author
Alexander G. Miamen
  • Function : Author
Roongruedee Chaiteerakij
  • Function : Author
Mengtao Zhou
  • Function : Author
Michael K. Asiedu
  • Function : Author
Catherine D. Moser
  • Function : Author
Shaoshan Han
  • Function : Author
Chunling Hu
  • Function : Author
Bubu A. Banini
  • Function : Author
Abdul M. Oseini
  • Function : Author
Yichun Chen
  • Function : Author
Yong Fang
  • Function : Author
Dongye Yang
  • Function : Author
Hassan M. Shaleh
  • Function : Author
Shaoqing Wang
  • Function : Author
Dehai Wu
  • Function : Author
Tao Song
  • Function : Author
Ju-Seog Lee
  • Function : Author
Snorri S. Thorgeirsson
  • Function : Author
Vijay H. Shah
  • Function : Author
Lewis R. Roberts
  • Function : Correspondent author

Abstract

Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice exhibited a markedly lower microvascular density. In human HCC cells, SULF2 overexpression increased endothelial proliferation, adhesion, chemotaxis, and tube formation in a paracrine fashion. Mechanistic analyses identified the extracellular matrix protein periostin (POSTN), a ligand of αvβ3/5 integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo The TGFβ1/SMAD pathway was identified as a critical signaling axis between SULF2 and upregulation of POSTN transcription. In clinical HCC specimens, elevated levels of SULF2 correlated with increased microvascular density, POSTN levels, and relatively poorer patient survival. Together, our findings define an important axis controlling angiogenesis in HCC and a mechanistic foundation for rational drug development. Cancer Res; 77(3); 632-45. ©2016 AACR.

Domains

Cancer

Dates and versions

hal-01485124 , version 1 (08-03-2017)

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Cite

Gang Chen, Ikuo Nakamura, Renumathy Dhanasekaran, Eriko Iguchi, Paola A. Romecin, et al.. Transcriptional Induction of Periostin by a Sulfatase 2-TGFβ1-SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma. Cancer Research, 2017, 77 (3), pp.632-645. ⟨10.1158/0008-5472.CAN-15-2556⟩. ⟨hal-01485124⟩
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