Regulation and functional significance of CDC42 alternative splicing in ovarian cancer

Oncotarget
Xiaolong HeJilai Yang

Abstract

Our previous study found that splicing factor polypyrimidine tract-binding protein 1 (PTBP1) had a role in tumorigenesis but the underlying mechanism remained unclear. In this study, we observed that knockdown of PTBP1 inhibited filopodia formation. Subsequently, we found that PTBP1 regulated the alternative splicing of CDC42, a major regulator of filopodia formation. Two CDC42 variants, CDC42-v1 and CDC42-v2, can be generated through alternative splicing. Knockdown of PTBP1 increased the expression of CDC42-v2. Ectopic expression of individual variants showed that CDC42-v2 suppressed filopodia formation, opposite to the effect of CDC42-v1. Quantitative RT-PCR revealed that CDC42-v2 was expressed at lower levels in ovarian cancer cell lines and ovarian tumor tissues than in normal control cells and tissues. Further, CDC42-v2 was observed to have inhibitory effects on ovarian tumor cell growth, colony formation in soft agar and invasiveness. In contrast, these inhibitory effects were not found with CDC42-v1. Taken together, above results suggest that the role of PTBP1 in tumorigenesis may be partly mediated by its regulation of CDC42 alternative splicing and CDC42-v2 might function as a tumor suppressor.

References

Jan 15, 1996·Genes & Development·H LouS M Berget
Nov 7, 2001·Current Biology : CB·S KrugmannA Hall
May 15, 2002·The EMBO Journal·Gilles GadéaPierre Roux
Mar 9, 2004·Trends in Cell Biology·Richard A Cerione
May 4, 2004·Molecular and Cellular Biology·Pedro Castelo-BrancoNick Proudfoot
Sep 24, 2005·Science·Florian C OberstrassFrédéric H-T Allain
Sep 9, 2006·Science·Tobias SjöblomVictor E Velculescu
Sep 13, 2006·The Journal of Cell Biology·Danijela VignjevicGary G Borisy
Feb 21, 2007·Nature Structural & Molecular Biology·Rotem KarniAdrian R Krainer
Aug 30, 2007·Nature Reviews. Genetics·Guey-Shin Wang, Thomas A Cooper
Feb 12, 2008·Current Protocols in Molecular Biology·Robert E KingstonJohn K Rose
Mar 8, 2008·Gastroenterology·Jolanda van HengelFrans van Roy
May 10, 2008·Nature Reviews. Molecular Cell Biology·Pieta K Mattila, Pekka Lappalainen
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak
Jun 19, 2008·Cellular Signalling·Soniya Sinha, Wannian Yang
Jun 24, 2008·Nature Reviews. Molecular Cell Biology·Antoine E Karnoub, Robert A Weinberg
Dec 19, 2008·Nature·Rujun KangAlaa El-Husseini
May 19, 2009·Nature Structural & Molecular Biology·Julian P VenablesSherif Abou Elela
Jun 10, 2009·Brain : a Journal of Neurology·Hannah C CheungGilbert J Cote
Jan 2, 2010·Nucleic Acids Research·Stefania Millevoi, Stéphan Vagner
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Cynthia V ClowerAdrian R Krainer
Jul 3, 2010·The Journal of Biological Chemistry·Emhonta JohnsonRuth A Keri
Aug 17, 2010·Nature Structural & Molecular Biology·Miriam LlorianChristopher W J Smith
Apr 26, 2011·Cellular Signalling·Kristy Stengel, Yi Zheng
Jun 28, 2011·Cell·Anne J Ridley
Sep 13, 2011·Nature·Kenichi YoshidaSeishi Ogawa
Sep 17, 2011·Nature Reviews. Genetics·Auinash Kalsotra, Thomas A Cooper
May 23, 2012·Cancer Discovery·Tsukasa ShibueRobert A Weinberg
Jul 24, 2012·Biochemical Society Transactions·Panagiota KafaslaChristopher W J Smith
Jan 30, 2013·Molecular and Cellular Biology·Akiyuki Nishimura, Maurine E Linder
Sep 26, 2013·The Biochemical Journal·Alexander WirthEvgeni Ponimaskin

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Citations

Jun 7, 2018·Biochemical Society Transactions·Xosé R Bustelo
Mar 3, 2020·Journal of Zhejiang University. Science. B·Wei ZhuCai-Ping Ren
May 18, 2018·Journal of Cell Science·R Eric BlueJimena Giudice
Oct 3, 2020·Journal of Cellular and Molecular Medicine·Zheng ZhaoFan Wu
Jan 6, 2021·IET Systems Biology·Hua-Yu WuShang-Ling Pan

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Methods Mentioned

BETA
GTPase
gene knockout
pulldown
transfection
PCR
Pull-Down
Assay

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