title: Par3 regulates invasion of pancreatic cancer cells via interaction with Tiam1.
abstract: The conserved polarity complex, which comprises partitioning-defective proteins Par3, Par6, and the atypical protein kinase C, affects various cell-polarization events, including assembly of tight junctions. Control of tight junction assembly is closely related to invasion and migration potential. However, as the importance of conserved polarity complexes in regulating pancreatic cancer invasion and metastasis is unclear, we investigated their role and mechanism in pancreatic cancers. We first detect that the key protein of the conserved polarity complex finds that only Par3 is down-regulated in pancreatic cancer tissues while Par6 and aPKC show no difference. What is more, Par3 tissues level was significantly and positively associated with patient overall survival. Knocking-down Par3 promotes pancreatic cancer cells invasion and migration. And Par3 requires interaction with Tiam1 to affect tight junction assembly, and then affect invasion and migration of pancreatic cancer cells. Then, we find that tight junction marker protein ZO-1 and claudin-1 are down-regulated in pancreatic cancer tissues. And the relationship of the expression of Par3 and ZO-1 in pancreatic cancer tissue is linear correlation. We establish liver metastasis model of human pancreatic cancer cells in Balb/c nude mice and find that knocking down Par3 promotes invasion and metastasis and disturbs tight junction assembly in vivo. Taken together, these results suggest that the Par3 regulates invasion and metastasis in pancreatic cancers by controlling tight junction assembly.
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Xingjun
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Chengjian
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Yechen
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China.
authors.forename: Ruizhi
authors.initials: R
authors.lastname: He
authors.affiliation: Department of Hepatic-Biliary-Pancreatic Surgery, Hubei Cancer Hospital, Wuhan City, People's Republic of China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Colon Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China. jinguxiong@gmail.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Tian
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China. ryqin@tjh.tjmu.edu.cn.
authors.forename: Renyi
authors.initials: R
authors.lastname: Qin
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000556:secondary; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1
chemical_list: D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; C471157:PARD3B protein, human; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human
keywords: Invasion; Pancreatic cancer; Par3; Tiam1; Tight junction