A peptide that inhibits function of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) reduces lung cancer metastasis

Ching-Hsien Chen, P. Thai, Ken Y Yoneda, K. B. Adler, P. C. Yang, Reen Wu

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Myristoylated Alanine-Rich C Kinase Substrate (MARCKS), a substrate of protein kinase C, is a key regulatory molecule controlling mucus granule secretion by airway epithelial cells as well as directed migration of leukocytes, stem cells and fibroblasts. Phosphorylation of MARKCS may be involved in these responses. However, the functionality of MARCKS and its related phosphorylation in lung cancer malignancy have not been characterized. This study demonstrated elevated levels of MARCKS and phospho-MARCKS in highly invasive lung cancer cell lines and lung cancer specimens from non-small-cell lung cancer patients. siRNA knockdown of MARCKS expression in these highly invasive lung cancer cell lines reduced cell migration and suppressed PI3K (phosphatidylinositol 3′-kinase)/Akt phosphorylation and Slug level. Interestingly, treatment with a peptide identical to the MARCKS N-terminus sequence (the MANS peptide) impaired cell migration in vitro and also the metastatic potential of invasive lung cancer cells in vivo. Mechanistically, MANS peptide treatment resulted in a coordination of increase of E-cadherin expression, suppression of MARCKS phosphorylation and AKT/Slug signalling pathway but not the expression of total MARCKS. These results indicate a crucial role for MARCKS, specifically its phosphorylated form, in potentiating lung cancer cell migration/metastasis and suggest a potential use of MARCKS-related peptides in the treatment of lung cancer metastasis.

Original languageEnglish (US)
Pages (from-to)3696-3706
Number of pages11
JournalOncogene
Volume33
Issue number28
DOIs
StatePublished - Jul 10 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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