title: Heterogeneous nuclear ribonucleoprotein K (hnRNP-K) promotes tumor metastasis by induction of genes involved in extracellular matrix, cell movement, and angiogenesis.
abstract: 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.
authors.affiliation: National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan.
authors.forename: Ran
authors.initials: R
authors.lastname: Gao
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inoue
authors.forename: Nashi
authors.initials: N
authors.lastname: Widodo
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D009363:Neoplasm Proteins
keywords: Angiogenesis; Cancer Biology; Cancer Tumor Promoter; Cell Growth; Cell Invasion; Cell Migration; Cell Proliferation; Cell Signaling; Tumor Metastases; hnRNP-K
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