2. Academic Validation
  3. SOX9 is a critical regulator of TSPAN8-mediated metastasis in pancreatic cancer

SOX9 is a critical regulator of TSPAN8-mediated metastasis in pancreatic cancer

  • Oncogene. 2021 Jul;40(30):4884-4893. doi: 10.1038/s41388-021-01864-9.
Junjian Li  # 1 2,  Xiaoliang Chen  # 3,  Liqun Zhu  # 4,  Zhenghong Lao  # 5,  Tianhao Zhou 2,  Lijuan Zang 6,  Weiyu Ge 2,  Mengyi Jiang 7,  Jingxuan Xu 2,  Yuan Cao 2,  Shaoqian Du 2,  Yue Yu 8,  Guangjian Fan 9,  Hongxia Wang 10
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, China.
  • 2 State Key Laboratory of Oncogenes and Related Genes, Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 The Center for Chronic Disease Control and Prevention, Shenzhen Guangming District Centers for Disease Control and Prevention, Shenzhen, China.
  • 4 Department of Oncology, Liyang People's Hospital, Liyang, China.
  • 5 Department of Oncology, Deqing People's Hospital, Huzhou, China.
  • 6 Pathology Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 7 Department of Medical Oncology, Shanghai Jiaotong University Affiliated Sixth People's Hospital East Campus, Shanghai, China.
  • 8 Shanghai Experimental School, Shanghai, China.
  • 9 Translational Medicine Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. gjfan@shsmu.edu.cn.
  • 10 State Key Laboratory of Oncogenes and Related Genes, Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. whx365@126.com.
  • # Contributed equally.
PMID: 34163029 DOI: 10.1038/s41388-021-01864-9
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the deadliest Cancer mainly owing to its proclivity to early metastasis and the lack of effective targeted therapeutic drugs. Hence, understanding the molecular mechanisms underlying early invasion and metastasis by PDAC is imperative for improving patient outcomes. The present study identified that upregulation of TSPAN8 expression in PDAC facilitates metastasis in vivo and in vitro. We found SOX9 as a key transcriptional regulator of TSPAN8 expression in response to EGF stimulation. SOX9 modulation was sufficient to positively regulate endogenous expression of TSPAN8, with concomitant in vitro phenotypic changes such as loss of cell-matrix adherence and increased invasion. Moreover, increased SOX9 and TSPAN8 levels were shown to correlate in human pancreatic Cancer specimens and downregulated in vitro by EGFR tyrosine kinase inhibitors. High expression of SOX9 and TSPAN8 has been associated with tumor stage, poor prognosis and poor patient survival in PDAC. In conclusion, this study highlights the importance of the EGF-SOX9-TSPAN8 signaling cascade in the control of PDAC invasion and implies that TSPAN8 may be a promising novel therapeutic target for the treatment of PDAC.

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