title: Integrin β6 serves as an immunohistochemical marker for lymph node metastasis and promotes cell invasiveness in cholangiocarcinoma.
abstract: Cholangiocarcinoma is a devastating malignancy that is notoriously difficult to diagnose and is associated with a high mortality. Despite extensive efforts to improve the diagnosis and treatment of this neoplasm, limited progress has been made. Integrin β6 is a subtype of integrin that is expressed exclusively on the surfaces of epithelial cells and is associated with a variety of tumors. In the present study, we investigated the expression and roles of integrin β6 in cholangiocarcinoma. β6 upregulation in cholangiocarcinoma was correlated with lymph node metastasis and distant metastasis. Moreover, integrin β6 was identified as a biomarker for the diagnosis of cholangiocarcinoma and an indicator of lymph node metastasis. Integrin β6 significantly promoted the proliferation, migration and invasion of cholangiocarcinoma cells. Furthermore, integrin β6 increased Rac1-GTPase, resulting in the upregulation of metalloproteinase-9 (MMP9) and F-actin polymerization. Taken together, our results indicate that integrin β6 promotes tumor invasiveness in a Rac1-dependent manner and is a potential biomarker for tumor metastasis. Integrin β6 may help to improve the diagnostic accuracy, and targeting β6 may be a novel strategy for the treatment of cholangiocarcinoma.
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: Siddhartha
authors.initials: S
authors.lastname: Biswas
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: Benjia
authors.initials: B
authors.lastname: Liang
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: Xueqing
authors.initials: X
authors.lastname: Zou
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: Liqun
authors.initials: L
authors.lastname: Shan
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: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Ruliang
authors.initials: R
authors.lastname: Fang
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Niu
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D018281:Cholangiocarcinoma / Q000473:pathology* / Q000556:secondary*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D039641:Integrin beta Chains / Q000032:analysis*; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000473:pathology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D015415:Biomarkers; D039641:Integrin beta Chains; C107953:RAC1 protein, human; C072170:integrin beta6; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D020830:rac1 GTP-Binding Protein