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J Cell Mol Med. 2018 Mar;22(3):1864-1872. doi: 10.1111/jcmm.13470. Epub 2018 Jan 25.

Identification of Sox6 as a regulator of pancreatic cancer development.

Jiang W1,2, Yuan Q3, Jiang Y4, Huang L1,2, Chen C1,2, Hu G1,2, Wan R1,2, Wang X1,2, Yang L1,2.

Author information

1
Department of Gastroenterology, School of Medicine, Shanghai General Hospital/First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
2
Shanghai Key Laboratory of Pancreatic Disease, School of Medicine, Institute of Pancreatic Disease, Shanghai Jiao Tong University, Shanghai, China.
3
Department of Gastroenterology, School of Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.
4
Department of Gastroenterology, The Central Hospital of Putuo District, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Pancreatic cancer (PC) is an aggressive malignancy associated with a poor prognosis and low responsiveness to chemotherapy and radiotherapy. Most patients with PC have metastatic disease at diagnosis, which partly accounts for the high mortality from this disease. Here, we explored the role of the transcription factor sex-determining region Y-box (Sox) 6 in the invasiveness of PC cells. We showed that Sox6 is down-regulated in patients with PC in association with metastatic disease. Sox6 overexpression suppressed PC cell proliferation and migration in vitro and tumour growth and liver metastasis in vivo. Sox6 inhibited epithelial-mesenchymal transition (EMT), and Akt signalling. Sox6 was shown to interact with the promoter of Twist1, a helix-loop-helix transcription factor involved in the induction of EMT, and to modulate the expression of Twist1 by recruiting histone deacetylase 1 to the promoter of the Twist1 gene. Twist1 overexpression reversed the effect of Sox6 on inhibiting EMT, confirming that the effect of Sox6 on suppressing tumour invasiveness is mediated by the modulation of Twist1 expression. These results suggest a novel mechanism underlying the aggressive behaviour of PC cells and identify potential therapeutic targets for the treatment of PC.

KEYWORDS:

epithelial-mesenchymal transition ; Sox6; Twist1; pancreatic cancer

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