Transforming Growth Factor-β-Induced RBFOX3 Inhibition Promotes Epithelial-Mesenchymal Transition of Lung Cancer Cells

被引:17
作者
Kim, Yong-Eun [1 ]
Kim, Jong Ok [2 ]
Park, Ki-Sun [1 ]
Won, Minho [3 ]
Kim, Kyoon Eon [1 ]
Kim, Kee K. [1 ]
机构
[1] Chungnam Natl Univ, Dept Biochem, Daejeon 34134, South Korea
[2] Catholic Univ Korea, Daejeon St Marys Hosp, Dept Pathol, Daejeon 34943, South Korea
[3] Chungnam Natl Univ, Dept Pharmacol, Coll Med, Daejeon 35015, South Korea
关键词
EMT; lung cancer; Rbfox family; Rbfox3; RNA-binding protein; TUMOR PROGRESSION; TGF-BETA; EXPRESSION; DIFFERENTIATION; METASTASIS;
D O I
10.14348/molcells.2016.0150
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The RNA-binding protein Rbfox3 is a well-known splicing regulator that is used as a marker for post-mitotic neurons in various vertebrate species. Although recent studies indicate a variable expression of Rbfox3 in non-neuronal tissues, including lung tissue, its cellular function in lung cancer remains largely unknown. Here, we report that the number of RBFOX3-positive cells in tumorous lung tissue is lower than that in normal lung tissue. As the transforming growth factor-beta (TGF-beta) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-beta 1 treatment inhibited RBFOX3 expression at the transcriptional level. Further, RBFOX3 depletion led to a change in the expression levels of a subset of proteins related to epithelial-mesenchymal transition (EMT), such as Ecadherin and Claudin-1, during TGF-beta 1-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-beta-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.
引用
收藏
页码:625 / 630
页数:6
相关论文
共 27 条
[1]   Genetic variants in RBFOX3 are associated with sleep latency [J].
Amin, Najaf ;
Allebrandt, Karla V. ;
van der Spek, Ashley ;
Mueller-Myhsok, Bertram ;
Hek, Karin ;
Teder-Laving, Maris ;
Hayward, Caroline ;
Esko, Tonu ;
van Mill, Josine G. ;
Mbarek, Hamdi ;
Watson, Nathaniel F. ;
Melville, Scott A. ;
Del Greco, Fabiola M. ;
Byrne, Enda M. ;
Oole, Edwin ;
Kolcic, Ivana ;
Chen, Ting-hsu ;
Evans, Daniel S. ;
Coresh, Josef ;
Vogelzangs, Nicole ;
Karjalainen, Juha ;
Willemsen, Gonneke ;
Gharib, Sina A. ;
Zgaga, Lina ;
Mihailov, Evelin ;
Stone, Katie L. ;
Campbell, Harry ;
Brouwer, Rutger Ww ;
Demirkan, Ayse ;
Isaacs, Aaron ;
Dogas, Zoran ;
Marciante, Kristin D. ;
Campbell, Susan ;
Borovecki, Fran ;
Luik, Annemarie I. ;
Li, Man ;
Hottenga, Jouke Jan ;
Huffman, Jennifer E. ;
van den Hout, Mirjam C. G. N. ;
Cummings, Steven R. ;
Aulchenko, Yuru S. ;
Gehrman, Philip R. ;
Uitterlinden, Andre G. ;
Wichmann, Heinz-Erich ;
Muller-Nurasyid, Martina ;
Fehrmann, Rudolf S. N. ;
Montgomery, Grant W. ;
Hofman, Albert ;
Kao, Wen Hong Linda ;
Oostra, Ben A. .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2016, 24 (10) :1488-1495
[2]   RBFOX2 protein domains and cellular activities [J].
Arya, Anurada D. ;
Wilson, David I. ;
Baralle, Diana ;
Raponi, Michaela .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2014, 42 :1180-1183
[3]   The RNA-binding protein Rbfox2: an essential regulator of EMT-driven alternative splicing and a mediator of cellular invasion [J].
Braeutigam, C. ;
Rago, L. ;
Rolke, A. ;
Waldmeier, L. ;
Christofori, G. ;
Winter, J. .
ONCOGENE, 2014, 33 (09) :1082-1092
[4]   Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation [J].
Carreira-Rosario, Arnaldo ;
Bhargava, Varsha ;
Hillebrand, Jens ;
Kollipara, Rahul K. ;
Ramaswami, Mani ;
Buszczakl, Michael .
DEVELOPMENTAL CELL, 2016, 36 (05) :562-571
[5]   Role of transforming growth factor-β signaling in cancer [J].
de Caestecker, MP ;
Piek, E ;
Roberts, AB .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (17) :1388-1402
[6]   RNA-binding proteins and post-transcriptional gene regulation [J].
Glisovic, Tina ;
Bachorik, Jennifer L. ;
Yong, Jeongsik ;
Dreyfuss, Gideon .
FEBS LETTERS, 2008, 582 (14) :1977-1986
[7]  
Gold LI, 1999, CRIT REV ONCOGENESIS, V10, P303
[8]   Molecular requirements for epithelial-mesenchymal transition during tumor progression [J].
Huber, MA ;
Kraut, N ;
Beug, H .
CURRENT OPINION IN CELL BIOLOGY, 2005, 17 (05) :548-558
[9]   Transforming growth factor-β in cancer and metastasis [J].
Jakowlew, Sonia B. .
CANCER AND METASTASIS REVIEWS, 2006, 25 (03) :435-457
[10]   A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG [J].
Jin, Y ;
Suzuki, H ;
Maegawa, S ;
Endo, H ;
Sugano, S ;
Hashimoto, K ;
Yasuda, K ;
Inoue, K .
EMBO JOURNAL, 2003, 22 (04) :905-912