Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 176, Issue 6, Pages 3050-3061Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2010.090539
Keywords
-
Categories
Funding
- National Science Council [NSC94-3114-P002-002-Y[3], NSC95-2320-B002-048, NSC97-3112-B-002-041]
- National Taiwan University Hospital [NTUH-96S617, NTUH-97A08-1]
Ask authors/readers for more resources
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, ERM-binding 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. (Am J Pathol 2010, 176:3050-3061; DOI: 10.2353/ajpath.2010.090539)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available