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Cytoplasmic Accumulation of Heterogeneous Nuclear Ribonucleoprotein K Strongly Promotes Tumor Invasion in Renal Cell Carcinoma Cells.

Abstract
Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a part of the ribonucleoprotein complex which regulates diverse biological events. While overexpression of hnRNP K has been shown to be related to tumorigenesis in several cancers, both the expression patterns and biological mechanisms of hnRNP K in renal cell carcinoma (RCC) cells remain unclear. In this study, we showed that hnRNP K protein was strongly expressed in selected RCC cell lines (ACHN, A498, Caki-1, 786-0), and knock-down of hnRNP K expression by siRNA induced cell growth inhibition and apoptosis. Based on immunohistochemical (IHC) analysis of hnRNP K expression in human clear cell RCC specimens, we demonstrated that there was a significant positive correlation between hnRNP K staining score and tumor aggressiveness (e.g., Fuhrman grade, metastasis). Particularly, the rate of cytoplasmic localization of hnRNP K in primary RCC with distant metastasis was significantly higher than that in RCC without metastasis. Additionally, our results indicated that the cytoplasmic distribution of hnRNP K induced by TGF-β stimulus mainly contributed to TGF-β-triggered tumor cell invasion in RCC cells. Dominant cytoplasmic expression of ectopic hnRNP K markedly suppressed the inhibition of invasion by knock-down of endogenous hnRNP K. The expression level of matrix metalloproteinase protein-2 was decreased by endogenous hnRNP K knock-down, and restored by ectopic hnRNP K. Therefore, hnRNP K may be a key molecule involved in cell motility in RCC cells, and molecular mechanism associated with the subcellular localization of hnRNP K may be a novel target in the treatment of metastatic RCC.
AuthorsTaiyo Otoshi, Tomoaki Tanaka, Kazuya Morimoto, Tatsuya Nakatani
JournalPloS one (PLoS One) Vol. 10 Issue 12 Pg. e0145769 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID26713736 (Publication Type: Journal Article)
Chemical References
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • Transforming Growth Factor beta
Topics
  • Apoptosis (drug effects)
  • Carcinoma, Renal Cell (pathology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cytoplasm (drug effects, metabolism)
  • Down-Regulation (drug effects)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Heterogeneous-Nuclear Ribonucleoprotein K (genetics, metabolism)
  • Humans
  • Kidney Neoplasms (pathology)
  • Mutation
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Protein Transport (drug effects)
  • Transforming Growth Factor beta (pharmacology)

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