Presentation Authors: Zhicong Chen*, Yonghao Zhan, Shiming He, Xuesong Li, Liqun Zhou, Beijing, China, People's Republic of
Introduction: Transgelin, a well-known actin-binding protein, implicates in different aspects of cancer development with series of controversial studies. The aberrant expression of transgelin has also been reported in bladder cancer. Here we sought to confirm the expression pattern of transgelin and figure out its exact function and mechanism in bladder cancer.
Methods: Total 137 paired (primary bladder cancer and adjacent non-malignant tissue) and 219 cancer paraffin specimens and 27 paired fresh specimens were obtained from Peking University First Hospital. The expression level of transgelin in bladder cancer was detected by qRT-PCR and immunohistochemistry and validated by online datasets. After the construction of transgelin overexpression and knockdown cell lines, cell proliferation, colony formation, migration, invasion, and invadopodia formation were assayed in vitro. While in vivo tumor metastasis was evaluated by intravenously injecting bladder cancer cells into nude mice. Downstream targets of transgelin were investigated by qRT-PCR, western blot and bioinformatics analysis of online datasets.
Results: Transgelin was highly expressed in bladder cancer and correlated with advanced tumor stage, lymphatic metastasis, and poor prognosis. Inhibition of transgelin repressed cell colony formation, migration, invasion and invadopodia formation in vitro. Inhibition also led to a decrease in the number and size of lung metastases in vivo. Meanwhile, overexpression of transgelin displayed the relevant phenotypes. Moreover, the TGF-induced invasion and invadopodia formation could be mitigated by the suppression of transgelin. Slug was also downregulated after knockdown of transgelin. Investigation of mRNA expression patterns showed that the epithelial mesenchymal transition and invadopodia formation related genes significantly increased in the patients with higher expression level of transgelin. And those upregulated genes were enriched in focal adhesion and ECM-receptor interaction pathway.
Conclusions: Taken together, transgelin is a promising novel prognosis biomarker in bladder cancer. That transgelin promotes bladder cancer invasion through regulating invadopodia formation may represent a target for clinical intervention.
Source of Funding: This work was supported by the National Key R&D Program of China (2016YFC0902601); the National Natural Science Foundation of China (81672546, 81602253, 81772703); the Natural Science Foundation of Beijing (71772219, 7152146); and the Innovative Fund for