Modulation of tumor cell migration, invasion and cell-matrix adhesion by human monopolar spindle-one-binder 2

Wu,Wenjuan; Zhang,Xizhi; Qin,Haonan; Peng,Wanxin; Xue,Qingyu; Lv,Houning; Zhang,Hua; Qiu,Yumei; Cheng,Haichao; Zhang,Yu; Yu,Zhiyong; Shen,Weigan

doi:10.3892/or.2015.3855

Modulation of tumor cell migration, invasion and cell-matrix adhesion by human monopolar spindle-one-binder 2

Authors:
- Wenjuan Wu
- Xizhi Zhang
- Haonan Qin
- Wanxin Peng
- Qingyu Xue
- Houning Lv
- Hua Zhang
- Yumei Qiu
- Haichao Cheng
- Yu Zhang
- Zhiyong Yu
- Weigan Shen
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Affiliations: School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, College of Biological and Chemical Engineering, Yangzhou Vocational University, Yangzhou, Jiangsu 225000, P.R. China
Published online on: March 16, 2015 https://doi.org/10.3892/or.2015.3855
Pages: 2495-2503

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Abstract

Human monopolar spindle-one-binder 2 (hMOB2) is a member of the hMOB family of proteins, and it has been reported to regulate the nuclear-Dbf2-related kinase (NDR) activation. However, the function of hMOB2 expression in tumor cell adhesion and motility has not been addressed. Herein, the lentiviral-mediated overexpression and the knockdown of hMOB2 in HepG2 and SMMC-7721 cells was established. It was demonstrated that overexpression of hMOB2 significantly reduced the cell motility and enhanced the cell-matrix adhesion, while the hMOB2 knockdown decreased not only the cell motility, but also the cell-matrix adhesion. Immunofluorescence results showed that both hMOB2 overexpression and knockdown altered assembly of the focal adhesions and the actin cytoskeleton rearrangement. Furthermore, the focal adhesion kinase (FAK)-Src-paxillin signal pathway activated by hMOB2 was confirmed to be involved in controlling the cell motility and the cell-matrix adhesion. These results demonstrated that the altered cell-matrix adhesion and cell motility induced by hMOB2 expression was caused by the assembly of focal adhesions as well as the actin cytoskeleton rearrangement through the activation of the FAK-Src-paxillin signal pathway, unveiling a novel mechanism of cell motility and cell-matrix adhesion regulation induced by hMOB2 expression.

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1	Hergovich A, Kohler RS, Schmitz D, Vichalkovski A, Cornils H and Hemmings BA: The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation. Curr Biol. 19:1692–1702. 2009. View Article : Google Scholar : PubMed/NCBI
2	Hergovich A: MOB control: Reviewing a conserved family of kinase regulators. Cell Signal. 23:1433–1440. 2011. View Article : Google Scholar : PubMed/NCBI
3	Stavridi ES, Harris KG, Huyen Y, Bothos J, Verwoerd PM, Stayrook SE, Pavletich NP, Jeffrey PD and Luca FC: Crystal structure of a human Mob1 protein: Toward understanding Mob-regulated cell cycle pathways. Structure. 11:1163–1170. 2003. View Article : Google Scholar : PubMed/NCBI
4	Ponchon L, Dumas C, Kajava AV, Fesquet D and Padilla A: NMR solution structure of Mob1, a mitotic exit network protein and its interaction with an NDR kinase peptide. J Mol Biol. 337:167–182. 2004. View Article : Google Scholar : PubMed/NCBI
5	Lai ZC, Wei X, Shimizu T, Ramos E, Rohrbaugh M, Nikolaidis N, Ho LL and Li Y: Control of cell proliferation and apoptosis by mob as tumor suppressor, mats. Cell. 120:675–685. 2005. View Article : Google Scholar : PubMed/NCBI
6	Mrkobrada S, Boucher L, Ceccarelli DF, Tyers M and Sicheri F: Structural and functional analysis of Saccharomyces cerevisiae Mob1. J Mol Biol. 362:430–440. 2006. View Article : Google Scholar : PubMed/NCBI
7	Ho LL, Wei X, Shimizu T and Lai ZC: Mob as tumor suppressor is activated at the cell membrane to control tissue growth and organ size in Drosophila. Dev Biol. 337:274–283. 2010. View Article : Google Scholar
8	Kohler RS, Schmitz D, Cornils H, Hemmings BA and Hergovich A: Differential NDR/LATS interactions with the human MOB family reveal a negative role for human MOB2 in the regulation of human NDR kinases. Mol Cell Biol. 30:4507–4520. 2010. View Article : Google Scholar : PubMed/NCBI
9	Tavares A, Gonçalves J, Florindo C, Tavares AA and Soares H: Mob1: Defining cell polarity for proper cell division. J Cell Sci. 125:516–527. 2012. View Article : Google Scholar : PubMed/NCBI
10	Chow A, Hao Y and Yang X: Molecular characterization of human homologs of yeast MOB1. Int J Cancer. 126:2079–2089. 2010.
11	Florindo C, Perdigão J, Fesquet D, Schiebel E, Pines J and Tavares AA: Human Mob1 proteins are required for cytokinesis by controlling microtubule stability. J Cell Sci. 125:3085–3090. 2012. View Article : Google Scholar : PubMed/NCBI
12	Wang ZX, Wang HY and Wu MC: Identification and characterization of a novel human hepatocellular carcinoma-associated gene. Br J Cancer. 85:1162–1167. 2001. View Article : Google Scholar : PubMed/NCBI
13	He Y, Emoto K, Fang X, Ren N, Tian X, Jan YN and Adler PN: Drosophila Mob family proteins interact with the related tricor-nered (Trc) and warts (Wts) kinases. Mol Biol Cell. 16:4139–4152. 2005. View Article : Google Scholar : PubMed/NCBI
14	Emoto K, He Y, Ye B, Grueber WB, Adler PN, Jan LY and Jan YN: Control of dendritic branching and tiling by the Tricornered-kinase/Furry signaling pathway in Drosophila sensory neurons. Cell. 119:245–256. 2004. View Article : Google Scholar : PubMed/NCBI
15	Liu LY, Lin CH and Fan SS: Function of Drosophila mob2 in photoreceptor morphogenesis. Cell Tissue Res. 338:377–389. 2009. View Article : Google Scholar : PubMed/NCBI
16	Lin CH, Hsieh M and Fan SS: The promotion of neurite formation in Neuro2A cells by mouse Mob2 protein. FEBS Lett. 585:523–530. 2011. View Article : Google Scholar : PubMed/NCBI
17	Stork O, Zhdanov A, Kudersky A, Yoshikawa T, Obata K and Pape HC: Neuronal functions of the novel serine/threonine kinase Ndr2. J Biol Chem. 279:45773–45781. 2004. View Article : Google Scholar : PubMed/NCBI
18	Akakura S and Gelman IH: Pivotal role of AKAP12 in the regulation of cellular adhesion dynamics: Control of cytoskeletal architecture, cell migration, and mitogenic signaling. J Signal Transduct. 2012:5291792012.PubMed/NCBI
19	Lock JG, Wehrle-Haller B and Strömblad S: Cell-matrix adhesion complexes: Master control machinery of cell migration. Semin Cancer Biol. 18:65–76. 2008. View Article : Google Scholar
20	Zong F, Fthenou E, Mundt F, Szatmári T, Kovalszky I, Szilák L, Brodin D, Tzanakakis G, Hjerpe A and Dobra K: Specific syndecan-1 domains regulate mesenchymal tumor cell adhesion, motility and migration. PLoS One. 6:e148162011. View Article : Google Scholar : PubMed/NCBI
21	Geiger B, Spatz JP and Bershadsky AD: Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol. 10:21–33. 2009. View Article : Google Scholar : PubMed/NCBI
22	Lanning NJ, Su HW, Argetsinger LS and Carter-Su C: Identification of SH2B1β as a focal adhesion protein that regulates focal adhesion size and number. J Cell Sci. 124:3095–3105. 2011. View Article : Google Scholar : PubMed/NCBI
23	Webb DJ, Donais K, Whitmore LA, Thomas SM, Turner CE, Parsons JT and Horwitz AF: FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol. 6:154–161. 2004. View Article : Google Scholar : PubMed/NCBI
24	Fraley SI, Feng Y, Krishnamurthy R, Kim DH, Celedon A, Longmore GD and Wirtz D: A distinctive role for focal adhesion proteins in three-dimensional cell motility. Nat Cell Biol. 12:598–604. 2010. View Article : Google Scholar : PubMed/NCBI
25	van Nimwegen MJ and van de Water B: Focal adhesion kinase: A potential target in cancer therapy. Biochem Pharmacol. 73:597–609. 2007. View Article : Google Scholar
26	Mitra SK and Schlaepfer DD: Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol. 18:516–523. 2006. View Article : Google Scholar : PubMed/NCBI
27	Ishikawa T and Kramer RH: Sdc1 negatively modulates carcinoma cell motility and invasion. Exp Cell Res. 316:951–965. 2010. View Article : Google Scholar :
28	Geiger B, Bershadsky A, Pankov R and Yamada KM: Transmembrane crosstalk between the extracellular matrix - cytoskeleton crosstalk. Nat Rev Mol Cell Biol. 2:793–805. 2001. View Article : Google Scholar : PubMed/NCBI
29	Hynes RO: Integrins: Bidirectional, allosteric signaling machines. Cell. 110:673–687. 2002. View Article : Google Scholar : PubMed/NCBI
30	Gupton SL and Waterman-Storer CM: Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration. Cell. 125:1361–1374. 2006. View Article : Google Scholar : PubMed/NCBI
31	Hotulainen P and Lappalainen P: Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J Cell Biol. 173:383–394. 2006. View Article : Google Scholar : PubMed/NCBI
32	Hall A: Rho GTPases and the actin cytoskeleton. Science. 279:509–514. 1998. View Article : Google Scholar : PubMed/NCBI
33	Ridley AJ: Rho GTPases and cell migration. J Cell Sci. 114:2713–2722. 2001.PubMed/NCBI
34	Machacek M, Hodgson L, Welch C, Elliott H, Pertz O, Nalbant P, Abell A, Johnson GL, Hahn KM and Danuser G: Coordination of Rho GTPase activities during cell protrusion. Nature. 461:99–103. 2009. View Article : Google Scholar : PubMed/NCBI
35	Liu J, Di G, Wu CT, Hu X and Duan H: CEACAM1 inhibits cell-matrix adhesion and promotes cell migration through regulating the expression of N-cadherin. Biochem Biophys Res Commun. 430:598–603. 2013. View Article : Google Scholar
36	Luo M and Guan JL: Focal adhesion kinase: A prominent determinant in breast cancer initiation, progression and metastasis. Cancer Lett. 289:127–139. 2010. View Article : Google Scholar :
37	Zhao J and Guan JL: Signal transduction by focal adhesion kinase in cancer. Cancer Metastasis Rev. 28:35–49. 2009. View Article : Google Scholar : PubMed/NCBI
38	Van Slambrouck S, Jenkins AR, Romero AE and Steelant WF: Reorganization of the integrin α2 subunit controls cell adhesion and cancer cell invasion in prostate cancer. Int J Oncol. 34:1717–1726. 2009. View Article : Google Scholar : PubMed/NCBI
39	Van Slambrouck S, Grijelmo C, De Wever O, Bruyneel E, Emami S, Gespach C and Steelant WF: Activation of the FAK-src molecular scaffolds and p130Cas-JNK signaling cascades by α1-integrins during colon cancer cell invasion. Int J Oncol. 31:1501–1508. 2007.PubMed/NCBI
40	Crosara-Alberto DP, Inoue RY and Costa CR: FAK signalling mediates NF-kappaB activation by mechanical stress in cardiac myocytes. Clin Chim Acta. 403:81–86. 2009. View Article : Google Scholar : PubMed/NCBI
41	Bjorge JD, Jakymiw A and Fujita DJ: Selected glimpses into the activation and function of Src kinase. Oncogene. 19:5620–5635. 2000. View Article : Google Scholar : PubMed/NCBI