title: Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation.
abstract: Cancer upregulated gene (CUG) 2, as a novel oncogene, has been predominantly detected in various cancer tissues, such as ovary, liver, lung and colon. We recently showed that CUG2 elevates STAT1 activity, leading to resistance to infection by oncolytic vesicular stomatitis virus. To investigate a possible role for CUG2-induced activation of STAT1 in oncogenesis, we first established a colon cancer cell line stably expressing CUG2 (Colon26L5-CUG2). Colon26L5-CUG2 exhibited higher levels not only in phosphorylation of STAT1, but also phosphorylation of Jak1/Tyk2 compared to that of the control (Colon26L5-Vec) cell line. Inhibition of Akt or ERK activity reduced phosphorylation of STAT1 in Colon26L5-CUG2 cells whereas inhibition of p38 MAPK did not significantly decrease levels of STAT1 phosphorylation, indicating that cell proliferation signals may be involved in CUG2-mediated activation of STAT1. Suppression of STAT1 expression diminished cell migration and wound healing compared to the control cells. In addition, since CUG2 expression conferred resistance to DNA damage caused by doxorubicin treatment, we investigated whether STAT1 is involved in resistance to doxorubicin-induced cell death. We found that STAT1 was not activated in Colon26L5-Vec cells while phosphorylated STAT1 was maintained in Colon26L5-CUG2 cells during doxorubicin treatment. Furthermore, suppression of STAT1 expression sensitized Colon26L5-CUG2 cells to doxorubicin-induced apoptosis whereas the control cells exhibited resistance to doxorubicin. Taken together, our results suggest that CUG2 enhances metastasis and drug resistance through STAT1 activation, which eventually contributes to tumor progression.
authors.affiliation: WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Waraporn
authors.initials: W
authors.lastname: Malilas
authors.forename: Sang Seok
authors.initials: SS
authors.lastname: Koh
authors.forename: Seokho
authors.initials: S
authors.lastname: Kim
authors.forename: Ratakorn
authors.initials: R
authors.lastname: Srisuttee
authors.forename: Il-Rae
authors.initials: IR
authors.lastname: Cho
authors.forename: Jeong
authors.initials: J
authors.lastname: Moon
authors.forename: Hwa-Seung
authors.initials: HS
authors.lastname: Yoo
authors.forename: Sangtaek
authors.initials: S
authors.lastname: Oh
authors.forename: Randal N
authors.initials: RN
authors.lastname: Johnston
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D002868:Chromosomal Proteins, Non-Histone; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D050794:STAT1 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D014945:Wound Healing / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C534000:CENPW protein, human; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D048051:p38 Mitogen-Activated Protein Kinases