title: HIC1 attenuates invasion and metastasis by inhibiting the IL-6/STAT3 signalling pathway in human pancreatic cancer.
abstract: Hypermethylated in cancer 1 (HIC1) is a tumour suppressor gene that is frequently deleted or epigenetically silenced in many human cancers. However, the molecular function of HIC1 in pancreatic cancer has not been fully elucidated, especially in cancer invasion and metastasis. We aimed to clarify the clinical relevance of HIC1 and human pancreatic cancer and the mechanism of its effect on invasion and metastasis .HIC1 was downregulated in pancreatic cancer patient cancer tissue and pancreatic cancer cell lines. A tissue microarray analysis demonstrated that negative HIC1 expression predicted advanced pathological stages and worse patient survival. In addition, HIC1 inhibited the invasion and metastasis of pancreatic cancer cells both in vitro and in vivo. Finally, HIC1 repressed the expression of STAT3 target genes, including c-Myc, VEGF, CyclinD1, MMP2 and MMP9, by binding and interacting with STAT3 to impede its DNA-binding ability but without affecting the protein levels of STAT3 and p-STAT3. Therefore, HIC1 appears to function as a STAT3 inhibitor and may be a promising target for cancer research and for the development of an optimal treatment approach for pancreatic cancer.
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of General Surgery, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China.
authors.forename: Kundong
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Pathology Center, Shanghai General Hospital/First People's Hospital/Faculty of Basic Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of General Surgery, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Pathology Center, Shanghai General Hospital/First People's Hospital/Faculty of Basic Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Tunike
authors.initials: T
authors.lastname: Mulatibieke
authors.affiliation: Pathology Center, Shanghai General Hospital/First People's Hospital/Faculty of Basic Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: richardwangxp@163.com.
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital/First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 HaiNing Road, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: huguoyongsh@sina.com.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Hu
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: C499808:HIC1 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D051741:Kruppel-Like Transcription Factors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: HIC1; IL-6/STAT3; Invasion; Metastasis; Pancreatic cancer