Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis

• Published in: PloS one 2016-02, Vol.11 (2), p.e0149028-e0149028
• Main Authors: Fan, Xiaoqiang, Zhang, Xiu, Shen, Jie, Zhao, Haibin, Yu, Xuetao, Chen, Yong'an, Zhuang, Zhuonan, Deng, Xiaolong, Feng, Hua, Wang, Yunfei, Peng, Long
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Animal models; Animals; Biology and Life Sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Cancer metastasis; Cell culture; Cell Line, Tumor; Cell Proliferation; Cell survival; Development and progression; Disease-Free Survival; Endoplasmic reticulum; Etiology; Female; Gene Expression; Gene Knockdown Techniques; Genes; Genetic aspects; Humans; Immunology; Liver; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; Liver Neoplasms - secondary; Lymphatic Metastasis; Male; Medical prognosis; Medical research; Medicine and Health Sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Nude; Middle Aged; mRNA; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Recurrence, Local - metabolism; Neoplasm Transplantation; NF-kappa B - metabolism; NF-κB protein; Oncology; Ovarian cancer; Pancreatic cancer; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pathogenesis; Physiological aspects; Prognosis; Proportional Hazards Models; Prostate; Proteins; Research and Analysis Methods; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Stress response; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumorigenesis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0149028

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.