SHP2 phosphatase as a novel therapeutic target for melanoma treatment

Ruo Yu Zhang, Zhi Hong Yu, Lifan Zeng, Sheng Zhang, Yunpeng Bai, Jinmin Miao, Lan Chen, Jingwu Xie, Zhong Yin Zhang

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Melanoma ranks among the most aggressive and deadly human cancers. Although a number of targeted therapies are available, they are effective only in a subset of patients and the emergence of drug resistance often reduces durable responses. Thus there is an urgent need to identify new therapeutic targets and develop more potent pharmacological agents for melanoma treatment. Herein we report that SHP2 levels are frequently elevated in melanoma, and high SHP2 expression is significantly associated with more metastatic phenotype and poorer prognosis. We show that SHP2 promotes melanoma cell viability, motility, and anchorage-independent growth, through activation of both ERK1/2 and AKT signaling pathways. We demonstrate that SHP2 inhibitor 11a-1 effectively blocks SHP2-mediated ERK1/2 and AKT activation and attenuates melanoma cell viability, migration and colony formation. Most importantly, SHP2 inhibitor 11a-1 suppresses xenografted melanoma tumor growth, as a result of reduced tumor cell proliferation and enhanced tumor cell apoptosis. Taken together, our data reveal SHP2 as a novel target for melanoma and suggest SHP2 inhibitors as potential novel therapeutic agents for melanoma treatment.

Original languageEnglish (US)
Pages (from-to)73817-73829
Number of pages13
JournalOncotarget
Volume7
Issue number45
DOIs
StatePublished - Jan 1 2016

Keywords

  • Drug discovery
  • Melanoma
  • Protein tyrosine phosphatase
  • SHP2
  • SHP2 inhibitor

ASJC Scopus subject areas

  • Oncology

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    Zhang, R. Y., Yu, Z. H., Zeng, L., Zhang, S., Bai, Y., Miao, J., Chen, L., Xie, J., & Zhang, Z. Y. (2016). SHP2 phosphatase as a novel therapeutic target for melanoma treatment. Oncotarget, 7(45), 73817-73829. https://doi.org/10.18632/oncotarget.12074