Podocalyxin EBP50 ezrin molecular complex enhances the metastatic potential of renal cell carcinoma through recruiting Rac1 guanine nucleotide exchange factor ARHGEF7

Yung Ho Hsu, Wei Ling Lin, Yi Ting Hou, Yeong Shiau Pu, Chia Tung Shun, Chi Ling Chen, Yih Yiing Wu, Jen Yau Chen, Tso Hsiao Chen, Tzuu Shuh Jou

Research output: Contribution to journalArticle

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Abstract

Podocalyxin was initially identified in glomerular podocytes to critically maintain the structural and functional integrity of the glomerular ultrafiltrative apparatus. Lately, it has emerged as a malignant marker in tumors arising from a variety of tissue origins. By immunohistochemistry, we identified that 9.6% of renal cell carcinoma patients overexpress this protein. This subset of patients had significantly shorter disease-specific and overall survivals, and, importantly, we established podocalyxin overexpression as an independent prognostic factor for latent distant metastasis with multivariate analysis. Podocalyxin down-regulation by small interfering RNA led to defective migration in model renal tubular cells, which was corrected by re-expression of podocalyxin. The activity of the small GTPase Rac1, a well-characterized modulator of cell migration, was diminished by podocalyxin knock-down. Conversely, podocalyxin overexpression in human embryonic kidney cells up-regulated Rac1 activity, which depended on a complex formed by podocalyxin, ERMbinding phosphoprotein 50, ezrin, and ARHGEF7, a Rac1 activator. Therefore, podocalyxin can serve as a biomarker to identify renal cell carcinoma patients with higher metastatic potential for more aggressive intervention at earlier clinical stages.

Original languageEnglish
Pages (from-to)3050-3061
Number of pages12
JournalAmerican Journal of Pathology
Volume176
Issue number6
DOIs
Publication statusPublished - 2010

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Guanine Nucleotide Exchange Factors
Renal Cell Carcinoma
Kidney
Podocytes
Monomeric GTP-Binding Proteins
ezrin
podocalyxin
Phosphoproteins
Tumor Biomarkers
Small Interfering RNA
Cell Movement
Down-Regulation
Multivariate Analysis
Biomarkers
Immunohistochemistry
Neoplasm Metastasis
Survival

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Podocalyxin EBP50 ezrin molecular complex enhances the metastatic potential of renal cell carcinoma through recruiting Rac1 guanine nucleotide exchange factor ARHGEF7. / Hsu, Yung Ho; Lin, Wei Ling; Hou, Yi Ting; Pu, Yeong Shiau; Shun, Chia Tung; Chen, Chi Ling; Wu, Yih Yiing; Chen, Jen Yau; Chen, Tso Hsiao; Jou, Tzuu Shuh.

In: American Journal of Pathology, Vol. 176, No. 6, 2010, p. 3050-3061.

Research output: Contribution to journalArticle

Hsu, Yung Ho ; Lin, Wei Ling ; Hou, Yi Ting ; Pu, Yeong Shiau ; Shun, Chia Tung ; Chen, Chi Ling ; Wu, Yih Yiing ; Chen, Jen Yau ; Chen, Tso Hsiao ; Jou, Tzuu Shuh. / Podocalyxin EBP50 ezrin molecular complex enhances the metastatic potential of renal cell carcinoma through recruiting Rac1 guanine nucleotide exchange factor ARHGEF7. In: American Journal of Pathology. 2010 ; Vol. 176, No. 6. pp. 3050-3061.
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