In Nov. 17 2018, Professor Tianhui Hu’s group published their new research “High expression of Tob1 indicates poor survival outcome and promotes tumour progression via a Wnt positive feedback loop in colon cancer” in Molecular Cancer (IF 7.776). This study, for the first time, discloses a new tumour promoting role and its related mechanism of Tob1, a tumour suppressor in other cancers, and provides new insight for prognosis and target therapy for colon cancer.
Tob1, a member of Tob/BTG anti-proliferative protein family, functions as a tumour suppressor in many cancers, including breast, pancreas, thyroid and gastric cancers. In those cancers, the nuclear localization of Tob1 is essential for its anti-tumour effect. However, the roles of Tob1 in colon cancer remain elusive. In this study, we found Tob1 expression was upregulated during colon cancer progression and significantly correlated with tumour size and tumour differentiation, and was a prognostic indicator in colon cancer. Unlike in other cancers where nuclear-localized Tob1 performs anti-cancer activity, Tob1 predominantly localizes in the cytosol of colon cancer cells where it bound and stabilized b-catenin to activate Wnt/b-catenin signaling, which in turn enhanced Tob1 expression, thus forming a positive feedback loop to promote cell proliferation. Moreover, Tob1 deficiency led to reduced tumorigenesis in AOM/DSS-treated mice and ApcMin/+ mice. Our findings provide important insights into a previously unrecognized oncogenic role of Tob1 in colon cancer, and implied Tob1 as an adverse prognostic factor and therapeutic target for colon cancer.
This study is supported by the National Natural Science Foundation of China and the Natural Science Foundation of Fujian Province, and is in collaboration with Professor Haibin Wang’s group and Xiamen Cancer Hospital, the First Affiliated Hospital of Xiamen University. The corresponding authors are Dr. Tianhui Hu, Yanyan Zhan and Haibin Wang. The co-first authors are Dandan Li and Xiao Li, two doctoral candidates of Medical College of Xiamen University.
Paper Link: https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-018-0907-9