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

doi:10.1016/j.prp.2019.01.027

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標題:	Association of nuclear localization of SHP2 and YAP1 with unfavorable prognosis in non-small cell lung cancer
作者:	Chen, Ming-Jenn(陳明鎮) Wang, Yao-Chen Wu, De-Wei Chen, Chi-Yi Lee, Huei
貢獻者:	Chi Mei Med Ctr, Dept Surg Chia Nan Univ Pharm & Sci, Coll Leisure & Recreat Management, Dept Sports Management Chung Shan Med Univ Hosp, Dept Internal Med Chung Shan Med Univ, Sch Med Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery
關鍵字:	SHP2 Prognosis NSCLC
日期:	2019-04
上傳時間:	2020-07-29 13:53:39 (UTC+8)
出版者:	ELSEVIER GMBH
摘要:	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/beta-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 < 0.001). Evaluation of cyclin Dl and c-Myc mRNA levels by the real-time reverse-phase polymerase chain reaction (RT-PCR) revealed that patients with high cyclin Dl and high c-Myc mRNA expressing tumors more commonly showed high nuclear YAP1 and high nuclear SHP2 (high/high) rather than the high/low, low/high, or low/low combinations (P < 0.001 for cyclin Dl and c-Myc). Kaplan-Meier and Cox-regression models showed OS and RFS to be poorer in patients in the high/high subgroup than in the low/low subgroup (OS: HR = 2.85, 95% CI, 1.52-5.35, P = 0.001; RFS: HR = 2.55, 95% CI, 1.37-4.72, P = 0.003). No prognostic significance was observed for the other two subgroups (low/high and high/low) when compared to the low/low subgroup in this study population. Therefore, we suggest that the prognostic value of SHP2 could reflect the nuclear localization of SHP2 and its interaction with nuclear YAP1, which led to subsequent upregulation of cyclin D1 and c-Myc mRNA expression via activation of the Wnt/beta-catenin signaling pathway.
關聯:	Pathology Research and Practice, v.215, n.4, pp.801-806
顯示於類別:	[藥學系(所)] 期刊論文

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