SHANK2 is a frequently amplified oncogene with evolutionarily conserved roles in regulating Hippo signaling.

SHANK2 is a frequently amplified oncogene with evolutionarily conserved roles in regulating Hippo signaling. Protein Cell. 2020 Jul 13;: Authors: Xu L, Li P, Hao X, Lu Y, Liu M, Song W, Shan L, Yu J, Ding H, Chen S, Yang A, Zeng YA, Zhang L, Jiang H Abstract Dysfunction of the Hippo pathway enables cells to evade contact inhibition and provides advantages for cancerous overgrowth. However, for a significant portion of human cancer, how Hippo signaling is perturbed remains unknown. To answer this question, we performed a genome-wide screening for genes that affect the Hippo pathway in Drosophila and cross-referenced the hit genes with human cancer genome. In our screen, Prosap was identified as a novel regulator of the Hippo pathway that potently affects tissue growth. Interestingly, a mammalian homolog of Prosap, SHANK2, is the most frequently amplified gene on 11q13, a major tumor amplicon in human cancer. Gene amplification profile in this 11q13 amplicon clearly indicates selective pressure for SHANK2 amplification. More importantly, across the human cancer genome, SHANK2 is the most frequently amplified gene that is not located within the Myc amplicon. Further studies in multiple human cell lines confirmed that SHANK2 overexpression causes deregulation of Hippo signaling through competitive binding for a LATS1 activator, and as a potential oncogene, SHANK2 promotes cellular transformation and tumor formation in vivo. In cancer cel...
Source: Protein and Cell - Category: Cytology Tags: Protein Cell Source Type: research