Mechanism of G0S2 in tumor dormancy and treatment relapse

Authors

• C Kieu
• A Ahad
• C Sellner
• Y Gu
• S Ratnayake
• F Leng
• D Meerzaman
• JY So
• L Yang

Abstract

TGF-β plays a critical role in immune and inflammatory regulation. Genetic deletion of Tgfbr2 in myeloid cells (Tgfbr2MyeKO) increased immune surveillance and decreased tumor metastasis in D2A1 breast cancer mouse models. Of particular interest, tumor cells in the metastatic lungs of Tgfbr2MyeKO mice were alive but remained dormant. Single-cell RNAseq from these tumor cells revealed a high G0/G1 switch gene 2 (G0S2) level, a mediator involved in the G0-G1 cell cycle transition. G0S2-positive tumor cells co-expressed dormant and quiescent markers, including Gas6, phosphor p38, and p27, suggesting evidence of dormant phenotype. Concerning the mechanism of G0S2 function, our data indicate that high G0S2 levels inhibit the G0 and G1 transitions in cell cycle progression. Furthermore, over-expression of G0S2 promoted cell cycle arrest in vitro and induced tumor dormancy in vivo. Deletion of G0S2 enhanced breast cancer cell proliferation. In human correlation studies, high G0S2 expression was associated with a poor survival rate in breast cancer-treated patients compared to the non-treated population. In conclusion, our study suggests that G0S2 is a critical mediator in regulating cell cycle arrest and the dormant state of tumor cells. Currently, we are investigating G0S2-interacting proteins and the potential role of G0S2 in treatment resistance and relapse.

Scientific Focus Area: Cancer Biology

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