Cancer is a leading cause of death and still awaits effective
therapies. Rapid industrialization has contributed to increase in incidence of
cancer. One of the reasons why most of the
cancers fail
therapy is due to their metastatic property. Hence identification of factors leading to
metastasis is highly important to design effective and novel anti-
cancer therapeutics. In our earlier study (Inoue, A., Sawata, S. Y., Taira, K., and Wadhwa, R. (2007) Loss-of-function screening by randomized intracellular
antibodies: identification of
hnRNP-K as a potential target for
metastasis. Proc. Natl. Acad. Sci. U.S.A. 104, 8983-8988), we had reported that the involvement of
heterogeneous nuclear ribonucleoprotein K (
hnRNP-K) in
metastasis. Here, we established
hnRNP-K-overexpressing and -underexpressing derivative cell lines and examined their proliferation and metastatic properties in vitro and in vivo. Whereas
hnRNP-K compromised cells showed delayed
tumor growth, its overexpression resulted in enhanced
malignancy and
metastasis. Molecular basis of the
hnRNP-K induced malignant and metastatic phenotypes was dissected by
cDNA microarray and pathway analyses. We found that the
hnRNP-K regulates extracellular matrix, cell motility, and angiogenesis pathways. Involvement of the selected genes (Cck,
Mmp-3,
Ptgs2, and Ctgf) and pathways was validated by gene-specific expression analysis. Our results demonstrated that the
hnRNP-K is a potential target for
metastasis therapy.