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
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
Externí odkaz: