title: Integrin β6 acts as an unfavorable prognostic indicator and promotes cellular malignant behaviors via ERK-ETS1 pathway in pancreatic ductal adenocarcinoma (PDAC).
abstract: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancers and is expected to become the second leading cause of cancer death by 2030. Despite extensive efforts to improve surgical treatment, limited progress has been made. Increasing evidence indicates that integrin β6 plays a crucial role in carcinoma invasion and metastasis. However, the expression and role of β6 in PDAC remain largely unknown. In the present study, we investigated the expression of β6 in PDAC and its potential value as a prognostic factor and therapeutic target. β6 upregulation was identified as an independent unfavorable prognostic indicator. Integrin β6 markedly promoted the proliferation and invasion of pancreatic carcinoma cells and induced ETS1 phosphorylation in an ERK-dependent manner, leading to the upregulation of matrix metalloprotease-9, which is essential for β6-mediated invasiveness of pancreatic carcinoma cells. Accordingly, small interfering RNA-mediated silencing of integrin β6 markedly suppressed xenograft tumor growth in vivo. Taken together, our results suggest that integrin β6 plays important roles in the progression of pancreatic carcinoma and contributes to reduced survival times, and may serve as a novel therapeutic target for the treatment of PDAC.
authors.affiliation: Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan, 250012, Shandong, China.
authors.forename: Zequn
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan, 250012, Shandong, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Lin
authors.affiliation: Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Thyroid & Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, 256603, Shandong, China.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China.
authors.forename: Jiayong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Niu
authors.affiliation: Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China. drniuweibo@163.com.
authors.forename: Weibo
authors.initials: W
authors.lastname: Niu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D039641:Integrin beta Chains / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C494041:ETS1 protein, human; D039641:Integrin beta Chains; D050784:Proto-Oncogene Protein c-ets-1; C072170:integrin beta6; D020780:Matrix Metalloproteinase 9
keywords: ETS1; Integrin β6; Invasiveness; PDAC; Prognostic indicator