EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis

S. Zhang, X. Wang, A. O. Osunkoya, S. Iqbal, Y. Wang, Z. Chen, S. Müller, Z. Chen, S. Josson, I. M. Coleman, P. S. Nelson, Y. A. Wang, R. Wang, D. M. Shin, F. F. Marshall, O. Kucuk, L. W.K. Chung, H. E. Zhau, Daqing Wu

Research output: Contribution to journalArticle

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Abstract

Epithelial-mesenchymal transition (EMT) is a crucial mechanism for the acquisition of migratory and invasive capabilities by epithelial cancer cells. By conducting quantitative proteomics in experimental models of human prostate cancer (PCa) metastasis, we observed strikingly decreased expression of EPLIN (epithelial protein lost in neoplasm; or LIM domain and actin binding 1, LIMA-1) upon EMT. Biochemical and functional analyses demonstrated that EPLIN is a negative regulator of EMT and invasiveness in PCa cells. EPLIN depletion resulted in the disassembly of adherens junctions, structurally distinct actin remodeling and activation of Β-catenin signaling. Microarray expression analysis identified a subset of putative EPLIN target genes associated with EMT, invasion and metastasis. By immunohistochemistry, EPLIN downregulation was also demonstrated in lymph node metastases of human solid tumors including PCa, breast cancer, colorectal cancer and squamous cell carcinoma of the head and neck. This study reveals a novel molecular mechanism for converting cancer cells into a highly invasive and malignant form, and has important implications in prognosis and treating metastasis at early stages.

Original languageEnglish (US)
Pages (from-to)4941-4952
Number of pages12
JournalOncogene
Volume30
Issue number50
DOIs
StatePublished - Dec 15 2011

Fingerprint

Epithelial-Mesenchymal Transition
Prostatic Neoplasms
Down-Regulation
Lymph Nodes
Neoplasm Metastasis
Actins
Neoplasms
Breast Neoplasms
Adherens Junctions
Catenins
Microarray Analysis
Proteomics
Colorectal Neoplasms
Theoretical Models
Epithelial Cells
Immunohistochemistry
Genes
Proteins

Keywords

  • EPLIN
  • cytoskeleton
  • epithelial-mesenchymal transition
  • lymph node metastasis
  • prostate cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. / Zhang, S.; Wang, X.; Osunkoya, A. O.; Iqbal, S.; Wang, Y.; Chen, Z.; Müller, S.; Chen, Z.; Josson, S.; Coleman, I. M.; Nelson, P. S.; Wang, Y. A.; Wang, R.; Shin, D. M.; Marshall, F. F.; Kucuk, O.; Chung, L. W.K.; Zhau, H. E.; Wu, Daqing.

In: Oncogene, Vol. 30, No. 50, 15.12.2011, p. 4941-4952.

Research output: Contribution to journalArticle

Zhang, S, Wang, X, Osunkoya, AO, Iqbal, S, Wang, Y, Chen, Z, Müller, S, Chen, Z, Josson, S, Coleman, IM, Nelson, PS, Wang, YA, Wang, R, Shin, DM, Marshall, FF, Kucuk, O, Chung, LWK, Zhau, HE & Wu, D 2011, 'EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis', Oncogene, vol. 30, no. 50, pp. 4941-4952. https://doi.org/10.1038/onc.2011.199
Zhang, S. ; Wang, X. ; Osunkoya, A. O. ; Iqbal, S. ; Wang, Y. ; Chen, Z. ; Müller, S. ; Chen, Z. ; Josson, S. ; Coleman, I. M. ; Nelson, P. S. ; Wang, Y. A. ; Wang, R. ; Shin, D. M. ; Marshall, F. F. ; Kucuk, O. ; Chung, L. W.K. ; Zhau, H. E. ; Wu, Daqing. / EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. In: Oncogene. 2011 ; Vol. 30, No. 50. pp. 4941-4952.
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