title: Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells.
abstract: Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein involved in transcription, mRNA splicing, mRNA stabilization and translation. Although hnRNP K has been suggested to play a role in the development of many cancers, its molecular function in colorectal cancer has remained elusive. Here we show that hnRNP K plays an important role in the mitotic process in HCT116 colon cancer cells. Furthermore, we demonstrate that hnRNP K directly transactivates the NUF2 gene, the product of which is a component of the NDC80 kinetochore complex and which is known to be critical for a stable spindle microtubule-kinetochore attachment. In addition, knockdown of both hnRNP K and NUF2 caused failure in metaphase chromosome alignment and drastic decrease in the growth of colon cancer cells. These results suggest that the hnRNP K-NUF2 axis is important for the mitotic process and proliferation of colon cancer cells and that this axis could be a target for the therapy of colon cancer.
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sugimasa
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
authors.forename: Kenzui
authors.initials: K
authors.lastname: Taniue
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan; Oncology Research Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kurimoto
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan. Electronic address: akiyama@iam.u-tokyo.ac.jp.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008807:Mice, Inbred BALB C; D008938:Mitosis; D011401:Promoter Regions, Genetic; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; C490197:NUF2 protein, human
keywords: Colorectal cancer; Heterogeneous nuclear ribonucleoprotein K (hnRNP K); NDC80 kinetochore complex component NUF2; Tumorigenicity