High expression of Tob1 indicates poor survival outcome and promotes tumour progression via a Wnt positive feedback loop in colon cancer
Autor: | Binbin Chen, Yuetan Ge, Tianhui Hu, Yan-yan Zhan, Yu Fu, Dandan Li, Li Xiao, Wenqing Zhang, Hanwei Cao, Haibin Wang |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cancer Research Protein family Colorectal cancer Gene Expression Tob1 Biology lcsh:RC254-282 law.invention 03 medical and health sciences Mice 0302 clinical medicine Prognostic marker Downregulation and upregulation law medicine Biomarkers Tumor Animals Humans Letter to the Editor Wnt Signaling Pathway Tumour-promoting Adaptor Proteins Signal Transducing Cell Proliferation Mice Knockout Wnt Positive Cell growth Wnt signaling pathway lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Prognosis Immunohistochemistry Colon cancer Cytosol Disease Models Animal 030104 developmental biology Cell Transformation Neoplastic Oncology ROC Curve 030220 oncology & carcinogenesis Colonic Neoplasms Cancer research Disease Progression Molecular Medicine Suppressor Wnt/β-catenin signaling |
Zdroj: | Molecular Cancer Molecular Cancer, Vol 17, Iss 1, Pp 1-6 (2018) |
ISSN: | 1476-4598 |
Popis: | Tob1, a Tob/BTG anti-proliferative protein family member, functions as a tumour suppressor in many cancers. Here, we reveal a unique oncogenic role of Tob1 in colon cancer. Tob1 expression was upregulated during colon cancer progression, was significantly correlated with tumour size and tumour differentiation, and was a prognostic indicator of colon cancer. Unlike in other cancers, where nuclear Tob1 performs anticancer activity, Tob1 is predominantly localized in the cytosol of colon cancer cells, where this protein binds and stabilizes β-catenin to activate Wnt/β-catenin signalling, which in turn enhances Tob1 expression, thus forming a positive feedback loop to promote cell proliferation. Moreover, Tob1 deficiency led to reduced tumourigenesis in AOM/DSS-treated and ApcMin/+ mice. Our findings provide important insights into a previously unrecognized oncogenic role of Tob1 in colon cancer and suggest that Tob1 is an adverse prognostic factor and therapeutic target for colon cancer. Electronic supplementary material The online version of this article (10.1186/s12943-018-0907-9) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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