Critical function for nuclear envelope protein TMEM209 in human pulmonary carcinogenesis.
Therapeutic targets for more effective and less toxic treatments of lung cancer remain important. Here we report the identification of the integral nuclear envelope protein TMEM209 as a critical driver of human lung cancer growth and survival. TMEM209 expression was normally limited to testis, but we found that it was widely expressed in lung cancer, in which it localized to the nuclear envelope, Golgi apparatus, and the cytoplasm of lung cancer cells. Ectopic overexpression of TMEM209 promoted cell growth, whereas TMEM209 attenuation was sufficient to block growth. Mass spectrometric analysis identified the nucleoporin protein NUP205 as a TMEM209-interacting protein, stabilizing NUP205 and increasing the level of c-Myc in the nucleus. Taken together, our findings indicate that TMEM209 overexpression and TMEM209-NUP205 interaction are critical drivers of lung cancer proliferation, suggesting a promising new target for lung cancer therapy.
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Takashi
T
Fujitomo
Yataro
Y
Daigo
Koichi
K
Matsuda
Koji
K
Ueda
Yusuke
Y
Nakamura
D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
C489427:MYC protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C576550:TMEM209 protein, human