Open AccessIdentification of Sox6 as a regulator of pancreatic cancer development
Author(s) -
Jiang Weiliang,
Yuan Qiongying,
Jiang Yuanye,
huang Li,
Chen Congying,
Hu Guoyong,
Wan Rong,
Wang Xingpeng,
Yang Lijuan
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13470
Subject(s) - cancer research , metastasis , transcription factor , epithelial–mesenchymal transition , twist transcription factor , biology , malignancy , pi3k/akt/mtor pathway , in vivo , medicine , cancer , pathology , signal transduction , microbiology and biotechnology , gene , biochemistry
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 .