Association of nuclear localization of SHP2 and YAP1 with unfavorable prognosis in non-small cell lung cancer

Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) is ubiquitously expressed in cytoplasmic localization, which in turn confers tumor malignancy and poor prognosis in various human cancers. YAP1 interacts with SHP2 to promote translocation of SHP2 to nucleus, which consequently promotes Wnt target activation. However, the oncogenic role of the nuclear localization of SHP2 in human cancers remains unclear. We hypothesized that nuclear SHP2 localization, in combination with nuclear YAP1 expression, could be associated with poor overall survival (OS) and relapse free survival (RFS) due to an increase in cyclin D1 and c-Myc mRNA expression following activation of Wnt/ß-catenin signaling. Immunohistochemical analysis of SHP2 and YAP1 protein expression in 102 tumors resected from patients with NSCLC revealed that nuclear SHP2 expression was well correlated with nuclear YAP1 expression (P