NME1L Negatively Regulates IGF1-Dependent Proliferation of Breast Cancer Cells

Dong Joo You, Sunam Mander, Cho Rong Park, Okjae Koo, Cheolju Lee, Seong Hyun Oh, Curie Ahn, Jae Young Seong, Jong-Ik Hwang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Non-metastatic cells 1 (NME1) or nm23 is the first metastasis suppressor gene discovered. It functions through various enzymatic activities and interacts with many intracellular proteins. The NME1 gene encodes two splicing variants, NME1 and NME1L. Most studies have focused on NME1 because of its abundance in cells. We previously reported NME1L-mediated suppression of NF-κB signaling by interacting with and inhibiting IKKβ. In this study, we demonstrated that NME1L, but not NME1, mediated inhibition of cell proliferation, although both NME1 and NME1L were involved in suppressing metastasis. A reporter gene assay was performed to determine the growth signaling pathway regulated by NME1L but none of the growth factors tested could induce an NF-κB-dependent luciferase expression except TNFα. Interestingly, SRE-reporter gene activation by IGF1 was significantly downregulated, along with reduction of ERK phosphorylation in NME1L expressing cells, compared to vector or NME1 expressing cells. NME1L directly interacted with KSR1, which is a scaffold for Raf-1, MEK, and ERK, that regulates ERK activation. Hence, NME1L plays a crucial role in regulation of cell proliferation by inhibiting IGF1-stimulated ERK phosphorylation through N-terminal 25 amino acid-mediated interaction with KSR1. J. Cell. Biochem. 117: 1454-1463, 2016.

Original languageEnglish
Pages (from-to)1454-1463
Number of pages10
JournalJournal of Cellular Biochemistry
Volume117
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

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Genes
Cells
Breast Neoplasms
Phosphorylation
Cell proliferation
Chemical activation
Mitogen-Activated Protein Kinase Kinases
Luciferases
Scaffolds
Assays
Intercellular Signaling Peptides and Proteins
Reporter Genes
Amino Acids
Cell Proliferation
Proteins
Tumor Suppressor Genes
Transcriptional Activation
Down-Regulation
Neoplasm Metastasis
Growth

Keywords

  • IGF1
  • KSR1
  • NME1L
  • PROLIFERATION

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

NME1L Negatively Regulates IGF1-Dependent Proliferation of Breast Cancer Cells. / You, Dong Joo; Mander, Sunam; Park, Cho Rong; Koo, Okjae; Lee, Cheolju; Oh, Seong Hyun; Ahn, Curie; Seong, Jae Young; Hwang, Jong-Ik.

In: Journal of Cellular Biochemistry, Vol. 117, No. 6, 01.06.2016, p. 1454-1463.

Research output: Contribution to journalArticle

You, Dong Joo ; Mander, Sunam ; Park, Cho Rong ; Koo, Okjae ; Lee, Cheolju ; Oh, Seong Hyun ; Ahn, Curie ; Seong, Jae Young ; Hwang, Jong-Ik. / NME1L Negatively Regulates IGF1-Dependent Proliferation of Breast Cancer Cells. In: Journal of Cellular Biochemistry. 2016 ; Vol. 117, No. 6. pp. 1454-1463.
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