Skip to main content
Erschienen in: Tumor Biology 2/2016

21.09.2015 | Original Article

Overexpression and biological function of TMEM48 in non-small cell lung carcinoma

verfasst von: Wenliang Qiao, Yudong Han, Wei Jin, Mi Tian, Pei Chen, Jie Min, Haiyang Hu, Binbin Xu, Wenzhuo Zhu, Liwen Xiong, Qiang Lin

Erschienen in: Tumor Biology | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

Transmembrane protein 48 (TMEM48), localized to nuclear pore complexes (NPCs), has been reported crucial for NPC assembly. Alterations in NPC members have been reported in several malignancies. The present study was aimed to elucidate the expression and biological function of TMEM48 in non-small cell lung carcinoma (NSCLC). Here, TMEM48 expression level was higher in NSCLC tissues than that in the adjacent normal tissues. Moreover, higher TMEM48 expression was correlated with a more advanced tumor stage, lymph node metastasis, bigger tumor size tumor stage, and shorter survival time. Knockdown of TMEM48 in NSCLC cell lines, A549 and H1299, inhibited cell proliferation and significantly increased cells population in G1 phase. Gene set enrichment analysis (GSEA) showed that cell cycle pathway was correlative with the TMEM48 expression. Additionally, real-time PCR and western blot analysis revealed that several cell cycle and DNA replication genes, including Cyclin B1, CDK1, CDC6, PCNA, and RCF4, were reduced after TMEM48 knockdown. Additionally, inhibition of TMEM48 in NSCLC cells significantly stimulated cell apoptosis, while notably repressed cell adhesion, migration, invasion, and tumorigenicity in nude mice. Our data provide insight into the biological relevance of TMEM48 in NSCLC progression and highlight its usefulness as a prognostic factor and potential therapeutic target in NSCLC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Cronshaw JM, Matunis MJ. The nuclear pore complex: disease associations and functional correlations. Trends Endocrinol Metab. 2004;15:34–9.CrossRefPubMed Cronshaw JM, Matunis MJ. The nuclear pore complex: disease associations and functional correlations. Trends Endocrinol Metab. 2004;15:34–9.CrossRefPubMed
3.
Zurück zum Zitat Agudo D, Gomez-Esquer F, Martinez-Arribas F, Nunez-Villar MJ, Pollan M, Schneider J. Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer. Int J Cancer. 2004;109:717–20.CrossRefPubMed Agudo D, Gomez-Esquer F, Martinez-Arribas F, Nunez-Villar MJ, Pollan M, Schneider J. Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer. Int J Cancer. 2004;109:717–20.CrossRefPubMed
4.
Zurück zum Zitat Kau TR, Way JC, Silver PA. Nuclear transport and cancer: from mechanism to intervention. Nat Rev Cancer. 2004;4:106–17.CrossRefPubMed Kau TR, Way JC, Silver PA. Nuclear transport and cancer: from mechanism to intervention. Nat Rev Cancer. 2004;4:106–17.CrossRefPubMed
5.
Zurück zum Zitat Poon IK, Jans DA. Regulation of nuclear transport: central role in development and transformation? Traffic (Copenhagen, Denmark). 2005;6:173–86.CrossRef Poon IK, Jans DA. Regulation of nuclear transport: central role in development and transformation? Traffic (Copenhagen, Denmark). 2005;6:173–86.CrossRef
6.
Zurück zum Zitat Stavru F, Hulsmann BB, Spang A, Hartmann E, Cordes VC, Gorlich D. Ndc1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes. J Cell Biol. 2006;173:509–19.CrossRefPubMedPubMedCentral Stavru F, Hulsmann BB, Spang A, Hartmann E, Cordes VC, Gorlich D. Ndc1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes. J Cell Biol. 2006;173:509–19.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Mansfeld J, Guttinger S, Hawryluk-Gara LA, Pante N, Mall M, Galy V, et al. The conserved transmembrane nucleoporin ndc1 is required for nuclear pore complex assembly in vertebrate cells. Mol Cell. 2006;22:93–103.CrossRefPubMed Mansfeld J, Guttinger S, Hawryluk-Gara LA, Pante N, Mall M, Galy V, et al. The conserved transmembrane nucleoporin ndc1 is required for nuclear pore complex assembly in vertebrate cells. Mol Cell. 2006;22:93–103.CrossRefPubMed
8.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
9.
Zurück zum Zitat Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, IARC. Tumours of the lung. In: Travis WD, editor. World Health Organization classification of tumours: pathology and genetics of tumours of the lung, pleura and heart. Lyon (France): IARC Press; 2004. p. 9–24. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, IARC. Tumours of the lung. In: Travis WD, editor. World Health Organization classification of tumours: pathology and genetics of tumours of the lung, pleura and heart. Lyon (France): IARC Press; 2004. p. 9–24.
10.
Zurück zum Zitat Kono SA, Marshall ME, Ware KE, Heasley LE. The fibroblast growth factor receptor signaling pathway as a mediator of intrinsic resistance to EGFR-specific tyrosine kinase inhibitors in non-small cell lung cancer. Drug Resist Updat. 2009;12:95–102.CrossRefPubMedPubMedCentral Kono SA, Marshall ME, Ware KE, Heasley LE. The fibroblast growth factor receptor signaling pathway as a mediator of intrinsic resistance to EGFR-specific tyrosine kinase inhibitors in non-small cell lung cancer. Drug Resist Updat. 2009;12:95–102.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Silletti S, Paku S, Raz A. Autocrine motility factor and the extracellular matrix. I. Coordinate regulation of melanoma cell adhesion, spreading and migration involves focal contact reorganization. Int J Cancer. 1998;76:120–8.CrossRefPubMed Silletti S, Paku S, Raz A. Autocrine motility factor and the extracellular matrix. I. Coordinate regulation of melanoma cell adhesion, spreading and migration involves focal contact reorganization. Int J Cancer. 1998;76:120–8.CrossRefPubMed
12.
Zurück zum Zitat Sun T, Du W, Xiong H, Yu Y, Weng Y, Ren L, et al. TMEFF2 deregulation contributes to gastric carcinogenesis and indicates poor survival outcome. Clin Cancer Res. 2014;20:4689–704.CrossRefPubMed Sun T, Du W, Xiong H, Yu Y, Weng Y, Ren L, et al. TMEFF2 deregulation contributes to gastric carcinogenesis and indicates poor survival outcome. Clin Cancer Res. 2014;20:4689–704.CrossRefPubMed
13.
Zurück zum Zitat Kapoor A, Yao W, Ying H, Hua S, Liewen A, Wang Q, et al. Yap1 activation enables bypass of oncogenic kras addiction in pancreatic cancer. Cell. 2014;158:185–97.CrossRefPubMedPubMedCentral Kapoor A, Yao W, Ying H, Hua S, Liewen A, Wang Q, et al. Yap1 activation enables bypass of oncogenic kras addiction in pancreatic cancer. Cell. 2014;158:185–97.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25:666–81.CrossRefPubMed Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25:666–81.CrossRefPubMed
15.
Zurück zum Zitat Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.CrossRef Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.CrossRef
16.
Zurück zum Zitat Nasmyth K. Control of the yeast cell cycle by the cdc28 protein kinase. Curr Opin Cell Biol. 1993;5:166–79.CrossRefPubMed Nasmyth K. Control of the yeast cell cycle by the cdc28 protein kinase. Curr Opin Cell Biol. 1993;5:166–79.CrossRefPubMed
17.
Zurück zum Zitat Liang C, Stillman B. Persistent initiation of DNA replication and chromatin-bound MCM proteins during the cell cycle in cdc6 mutants. Genes Dev. 1997;11:3375–86.CrossRefPubMedPubMedCentral Liang C, Stillman B. Persistent initiation of DNA replication and chromatin-bound MCM proteins during the cell cycle in cdc6 mutants. Genes Dev. 1997;11:3375–86.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Dietrich DR. Toxicological and pathological applications of proliferating cell nuclear antigen (pcna), a novel endogenous marker for cell proliferation. CRC Crit Rev Toxicol. 1993;23:77–109.CrossRef Dietrich DR. Toxicological and pathological applications of proliferating cell nuclear antigen (pcna), a novel endogenous marker for cell proliferation. CRC Crit Rev Toxicol. 1993;23:77–109.CrossRef
19.
Zurück zum Zitat Reynolds N, Fantes PA, MacNeill SA. A key role for replication factor c in DNA replication checkpoint function in fission yeast. Nucleic Acids Res. 1999;27:462–9.CrossRefPubMedPubMedCentral Reynolds N, Fantes PA, MacNeill SA. A key role for replication factor c in DNA replication checkpoint function in fission yeast. Nucleic Acids Res. 1999;27:462–9.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Gross A, McDonnell JM, Korsmeyer SJ. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13:1899–911.CrossRefPubMed Gross A, McDonnell JM, Korsmeyer SJ. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13:1899–911.CrossRefPubMed
21.
Zurück zum Zitat Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer. 2005;5:876–85.CrossRefPubMed Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer. 2005;5:876–85.CrossRefPubMed
22.
Zurück zum Zitat Leber MF, Efferth T. Molecular principles of cancer invasion and metastasis (review). Int J Oncol. 2009;34:881–95.PubMed Leber MF, Efferth T. Molecular principles of cancer invasion and metastasis (review). Int J Oncol. 2009;34:881–95.PubMed
23.
Zurück zum Zitat Antonin W, Ellenberg J, Dultz E. Nuclear pore complex assembly through the cell cycle: regulation and membrane organization. FEBS Lett. 2008;582:2004–16.CrossRefPubMed Antonin W, Ellenberg J, Dultz E. Nuclear pore complex assembly through the cell cycle: regulation and membrane organization. FEBS Lett. 2008;582:2004–16.CrossRefPubMed
Metadaten
Titel
Overexpression and biological function of TMEM48 in non-small cell lung carcinoma
verfasst von
Wenliang Qiao
Yudong Han
Wei Jin
Mi Tian
Pei Chen
Jie Min
Haiyang Hu
Binbin Xu
Wenzhuo Zhu
Liwen Xiong
Qiang Lin
Publikationsdatum
21.09.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4014-x

Weitere Artikel der Ausgabe 2/2016

Tumor Biology 2/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.