Researchers Identify VGLL4 as a Novel Tumor Suppressor in Lung Cancer

Lung cancer is one of the most devastating diseases worldwide. Its high incidence and mortality is mainly attributable to the poor understanding of the mechanisms involved in lung tumorigenesiss. Hippo pathway is a conserved regulator of organ size in both Drosophila and mammals. Emerging evidences have indicated the significance of Hippo pathway in cancer development.

Under the supervision of Prof. JI Hongbin, Prof. ZHANG Lei and Prof. ZHOU Zhaocai from the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, ZHANG Wenjing and her colleagues have found that VGLL4 suppresses lung cancer progression by negatively regulating YAP-TEAD transcriptional activity. Their work reveals that VGLL4 is frequently lowly expressed in both mouse and human lung cancer. Taking advantage of de novo lung cancer mouse model and human cancer cell lines, they clearly show that VGLL4 exhibits a strong inhibitory role in lung cancer growth and progression.

Mechanistic studies further show that VGLL4 inhibits the activity of the YAP-TEADs transcriptional complex. VGLL4 directly competes with YAP in binding to TEADs through two TDU domains. This study not only identifies VGLL4 as a new tumor suppressor in lung tumorigenesis, but also uncovers VGLL4 as an important modulator of Hippo pathway. Moreover, this work may also provide a new strategy for future lung cancer treatment.

This work entitled “VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex” was published online in Cell Research on January 24, 2014. This work was supported by grants from Ministry of Science and Technology of China, the Cross and Cooperation in Science and Technology Innovation Team program, the Strategic Priority Research Program of the CAS, the National Natural Science Foundation of China, Postdoctor Research Program of Shanghai Institutes for Biological Sciences, China Postdoctoral Science Foundation.