S100 Calcium Binding Protein A16 Promotes Cell Proliferation by triggering LATS1 ubiquitin degradation mediated by CUL4A ligase to inhibit Hippo pathway in Glioma development.

Yifang Hu, Rihua Zhang, Shan Lu, Wensong Zhang, Dan Wang, Yaoqi Ge, Feng Jiang, Xiaoxuan Qin, Yun Liu

International journal of biological sciences 2023

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Background: S100 Calcium Binding Protein A16 (S100A16), a novel member of S100 protein family, is linked to tumorigenic processes and abundantly expressed in CNS tissues. Our study aimed to explore the biological function and possible mechanism of S100A16 in the progression of glioma. Methods: Sequence data of S100A16 and survival prognosis of glioma patients were initially analyzed using public databases. Glioma tissues were collected to examine S100A16 expression levels. Glioma cell lines and nude mice were subjected to in vitro and in vivo functional experiments. Western blot, immunofluorescence (IF), immunoprecipitation (IP) and ubiquitination assays were done to further elucidate the underlying mechanism. Results: This study firstly revealed that S100A16 was markedly up-regulated in glioma, and patients with higher S100A16 levels have a shorter survival time. S100A16 overexpression promoted the proliferation, invasion and migration of glioma cells, and the tumor formation of nude mice. Importantly, we identified S100A16 as a negative regulator of the Hippo pathway which could decrease LATS1 expression levels, promote the YAP nuclear import and initiate the downstream target genes CYR61 and CTGF. Moreover, our data showed that S100A16 destabilized LATS1 protein by inducing the CUL4A-mediated LATS1 ubiquitination degradation. Conclusions: This study demonstrated a vital biological role of S100A16 in glioma progression mechanism by promoting CUL4A-mediated LATS1 ubiquitination to inhibit Hippo signaling pathway. S100A16 could be a novel biomarker and treatment option for glioma patients. © The author(s).

Citation

Yifang Hu, Rihua Zhang, Shan Lu, Wensong Zhang, Dan Wang, Yaoqi Ge, Feng Jiang, Xiaoxuan Qin, Yun Liu. S100 Calcium Binding Protein A16 Promotes Cell Proliferation by triggering LATS1 ubiquitin degradation mediated by CUL4A ligase to inhibit Hippo pathway in Glioma development. International journal of biological sciences. 2023;19(7):2034-2052