title: Decreased TIP30 expression predicts poor prognosis in pancreatic cancer patients.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive growth, and is characterized by early tissue invasion and metastasis with poor prognosis. Identifying prognostic markers and delineating the underlying mechanisms that promote progression of PDAC are important for the treatment of pancreatic cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple processes during tumor development and metastasis. Here, we investigated the expression of TIP30 in PDAC and its prognostic value in PDAC patients. We examined the expression of TIP30 by immunohistochemistry in tissue microarrays containing 106 surgically resected PDAC. Kaplan-Meier analysis and Cox proportional hazards regression modeling analysis showed that TIP30 expression independently predicted better survival in pancreatectomy patients (p < 0.01). Moreover, decreased TIP30 expression was associated with lymph node metastasis (p < 0.05) and loss of E-cadherin expression (r = 0.329, p < 0.01). Suppression of TIP30 resulted in upregulation of Snail and subsequent downregulation of E-cadherin in SW1990 cells containing high-level of endogenous TIP30. However, in the PANC-1 cells containing low level of endogenous TIP30, suppressing TIP30 caused upregulation of Slug instead of Snail, followed by upregulation of MMP9 rather than E-cadherin. Taken together, our work reveals that decreased TIP30 expression is able to enhance invasion and metastasis of pancreatic cancer cells through upregulation of the Snail family members and may serve as an independent predictor for poor outcomes in PDAC patients.
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China; Department of general surgery, Changhai Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Jing
authors.forename: Xiangui
authors.initials: X
authors.lastname: Hu
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zhou
authors.forename: Lianjie
authors.initials: L
authors.lastname: Liu
authors.forename: Minhui
authors.initials: M
authors.lastname: Zhu
authors.forename: Fan
authors.initials: F
authors.lastname: Yin
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014945:Wound Healing
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D012333:RNA, Messenger; D014157:Transcription Factors; D000123:Acetyltransferases; C111246:HTATIP2 protein, human
keywords: 30-kDa Tat-interacting protein; Snail family members; epithelia-mesenchymal transition; metastasis; pancreatic cancer; prognosis