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

doi:10.1038/onc.2011.199

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

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

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 language	English (US)
Pages (from-to)	4941-4952
Number of pages	12
Journal	Oncogene
Volume	30
Issue number	50
DOIs	https://doi.org/10.1038/onc.2011.199
State	Published - Dec 15 2011

Keywords

EPLIN
cytoskeleton
epithelial-mesenchymal transition
lymph node metastasis
prostate cancer

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/onc.2011.199

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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, D. (2011). EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. Oncogene, 30(50), 4941-4952. https://doi.org/10.1038/onc.2011.199

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

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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.",

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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