title: Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis.
abstract: Pancreatic cancer is an aggressive disease with dismal prognosis. It is of paramount importance to understand the underlying etiological mechanisms and identify novel, consistent, and easy-to-apply prognostic factors for precision therapy. TUSC3 (tumor suppressor candidate 3) was identified as a potential tumor suppressor gene and previous study showed TUSC3 is decreased in pancreatic cancer at mRNA level, but its putative tumor suppressor function remains to be verified. In this study, TUSC3 expression was found to be suppressed both at mRNA and protein levels in cell line models as well as in clinical samples; decreased TUSC3 expression was associated with higher pathological TNM staging and poorer outcome. In three pairs of cell lines with different NF-κB activity, TUSC3 expression was found to be reversely correlated with NF-κB activity. TUSC3-silenced pancreatic cancer cell line exhibited enhanced potential of proliferation, migration and invasion. In an orthotopic implanted mice model, TUSC3 silenced cells exhibited more aggressive phenotype with more liver metastasis. In conclusion, the current study shows that decreased immunological TUSC3 staining is a factor prognostic of poor survival in pancreatic cancer patients and decreased TUSC3 promotes pancreatic cancer cell proliferation, invasion and metastasis. The reverse correlation between NF-κB activity and TUSC3 expression may suggest a novel regulation pattern for this molecule.
authors.affiliation: Department of Oncology, Jimin Hospital, Shanghai, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Oncology, Jimin Hospital, Shanghai, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Jimin Hospital, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Pathology, Taihu Hospital, Wuxi, Jiangsu Province, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Jimin Hospital, Shanghai, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Oncology, Jimin Hospital, Shanghai, China.
authors.forename: Yong'an
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Shandong University Affiliated Qilu Hospital, Ji'nan, Shandong Province, China.
authors.forename: Zhuonan
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Department of Oncology, Jimin Hospital, Shanghai, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Oncology, Jimin Hospital, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Oncology, Jimin Hospital, Shanghai, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, Jimin Hospital, Shanghai, China.
authors.forename: Long
authors.initials: L
authors.lastname: Peng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins