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.