Abnormal expression of leiomyoma cytoskeletal proteins involved in cell migration

Ura,Blendi; Scrimin,Federica; Arrigoni,Giorgio; Athanasakis,Emmanouil; Aloisio,Michelangelo; Monasta,Lorenzo; Ricci,Giuseppe

doi:10.3892/or.2016.4688

Abnormal expression of leiomyoma cytoskeletal proteins involved in cell migration

Authors:
- Blendi Ura
- Federica Scrimin
- Giorgio Arrigoni
- Emmanouil Athanasakis
- Michelangelo Aloisio
- Lorenzo Monasta
- Giuseppe Ricci
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Affiliations: Institute for Maternal and Child Health - IRCCS ‘Burlo Garofolo’, Trieste, Italy, Department of Biomedical Sciences, University of Padova, Padova, Italy
Published online on: March 17, 2016 https://doi.org/10.3892/or.2016.4688
Pages: 3094-3100

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Abstract

Uterine leiomyomas are monoclonal tumors. Several factors are involved in the neoplastic transformation of the myometrium. In our study we focused on dysregulated cytoskeletal proteins in the leiomyoma as compared to the myometrium. Paired tissue samples of ten leiomyomas and adjacent myometria were obtained and analyzed by two‑dimensional gel electrophoresis (2-DE). Mass spectrometry was used for protein identification, and western blotting for 2-DE data validation. The values of ten cytoskeletal proteins were found to be significantly different: eight proteins were upregulated in the leiomyoma and two proteins were downregulated. Three of the upregulated proteins (myosin regulatory light polypeptide 9, four and a half LIM domains protein 1 and LIM and SH3 domain protein 1) are involved in cell migration, while downregulated protein transgelin is involved in replicative senescence. Myosin regulatory light polypeptide 9 (MYL9) was further validated by western blotting because it is considered to be a cell migration marker in several cancers and could play a key role in leiomyoma development. Our data demonstrate significant alterations in the expression of cytoskeletal proteins involved in leiomyoma growth. A better understanding of the involvement of cytoskeletal proteins in leiomyoma pathogenesis may contribute to the identification of new therapeutic targets and the development of new pharmacological approaches.

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1	Rein MS: Advances in uterine leiomyoma research: The progesterone hypothesis. Environ Health Perspect. 108(Suppl 5): 791–793. 2000. View Article : Google Scholar : PubMed/NCBI
2	Catherino WH and Malik M: Uterine leiomyomas express a molecular pattern that lowers retinoic acid exposure. Fertil Steril. 87:1388–1398. 2007. View Article : Google Scholar : PubMed/NCBI
3	Arslan AA, Gold LI, Mittal K, Suen TC, Belitskaya-Levy I, Tang MS and Toniolo P: Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: New evidence and a systematic review. Hum Reprod. 20:852–863. 2005. View Article : Google Scholar : PubMed/NCBI
4	Leppert PC, Jayes FL and Segars JH: The extracellular matrix contributes to mechanotransduction in uterine fibroids. Obstet Gynecol Int. 2014:7832892014. View Article : Google Scholar : PubMed/NCBI
5	Davis BJ, Risinger JI, Chandramouli GV, Bushel PR, Baird DD and Peddada SD: Gene expression in uterine leiomyoma from tumors likely to be growing (from black women over 35) and tumors likely to be non-growing (from white women over 35). PLoS One. 8:e639092013. View Article : Google Scholar : PubMed/NCBI
6	Wang Y, Feng G, Wang J, Zhou Y, Liu Y, Shi Y, Zhu Y, Lin W, Xu Y and Li Z: Differential effects of tumor necrosis factor-α on matrix metalloproteinase-2 expression in human myometrial and uterine leiomyoma smooth muscle cells. Hum Reprod. 30:61–70. 2015. View Article : Google Scholar
7	Elosegui-Artola A, Bazellières E, Allen MD, Andreu I, Oria R, Sunyer R, Gomm JJ, Marshall JF, Jones JL, Trepat X, et al: Rigidity sensing and adaptation through regulation of integrin types. Nat Mater. 13:631–637. 2014. View Article : Google Scholar : PubMed/NCBI
8	Vincent S and Settleman J: The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. Mol Cell Biol. 17:2247–2256. 1997. View Article : Google Scholar : PubMed/NCBI
9	Luo XG, Zhang CL, Zhao WW, Liu ZP, Liu L, Mu A, Guo S, Wang N, Zhou H and Zhang TC: Histone methyltransferase SMYD3 promotes MRTF-A-mediated transactivation of MYL9 and migration of MCF-7 breast cancer cells. Cancer Lett. 344:129–137. 2014. View Article : Google Scholar
10	Ura B, Scrimin F, Zanconati F, Arrigoni G, Monasta L, Romano A, Banco R, Zweyer M, Milani D and Ricci G: Two-dimensional gel electrophoresis analysis of the leiomyoma interstitial fluid reveals altered protein expression with a possible involvement in pathogenesis. Oncol Rep. 33:2219–2226. 2015.PubMed/NCBI
11	Norian JM, Owen CM, Taboas J, Korecki C, Tuan R, Malik M, Catherino WH and Segars JH: Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma. Matrix Biol. 31:57–65. 2012. View Article : Google Scholar
12	Mischiati C, Ura B, Roncoroni L, Elli L, Cervellati C, Squerzanti M, Conte D, Doneda L, Polverino de Laureto P, de Franceschi G, et al: Changes in protein expression in two cholangiocarcinoma cell lines undergoing formation of multi-cellular tumor spheroids in vitro. PLoS One. 10:e01189062015. View Article : Google Scholar
13	Lv J, Zhu X, Dong K, Lin Y, Hu Y and Zhu C: Reduced expression of 14-3-3 γ in uterine leiomyoma as identified by proteomics. Fertil Steril. 90:1892–1898. 2008. View Article : Google Scholar
14	Mouw JK, Yui Y, Damiano L, Bainer RO, Lakins JN, Acerbi I, Ou G, Wijekoon AC, Levental KR, Gilbert PM, et al: Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat Med. 20:360–367. 2014. View Article : Google Scholar : PubMed/NCBI
15	Butcher DT, Alliston T and Weaver VM: A tense situation: Forcing tumour progression. Nat Rev Cancer. 9:108–122. 2009. View Article : Google Scholar : PubMed/NCBI
16	Cooper JA: The role of actin polymerization in cell motility. Annu Rev Physiol. 53:585–605. 1991. View Article : Google Scholar : PubMed/NCBI
17	Salama SA, Kamel MW, Botting S, Salih SM, Borahay MA, Hamed AA, Kilic GS, Saeed M, Williams MY and Diaz-Arrastia CR: Catechol-o-methyltransferase expression and 2-methoxyestradiol affect microtubule dynamics and modify steroid receptor signaling in leiomyoma cells. PLoS One. 4:e73562009. View Article : Google Scholar : PubMed/NCBI
18	Ganguly A, Yang H and Cabral F: Class III β-tubulin counteracts the ability of paclitaxel to inhibit cell migration. Oncotarget. 2:368–377. 2011. View Article : Google Scholar : PubMed/NCBI
19	Roeder HA, Cramer SF and Leppert PC: A look at uterine wound healing through a histopathological study of uterine scars. Reprod Sci. 19:463–473. 2012. View Article : Google Scholar : PubMed/NCBI
20	Brown S, McGrath MJ, Ooms LM, Gurung R, Maimone MM and Mitchell CA: Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1. Localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication. J Biol Chem. 274:27083–27091. 1999. View Article : Google Scholar : PubMed/NCBI
21	Robinson PA, Brown S, McGrath MJ, Coghill ID, Gurung R and Mitchell CA: Skeletal muscle LIM protein 1 regulates integrin-mediated myoblast adhesion, spreading, and migration. Am J Physiol Cell Physiol. 284:C681–C695. 2003. View Article : Google Scholar
22	Huveneers S and Danen EH: Adhesion signaling - crosstalk between integrins, Src and Rho. J Cell Sci. 122:1059–1069. 2009. View Article : Google Scholar : PubMed/NCBI
23	Liao XH, Wang N, Liu LY, Zheng L, Xing WJ, Zhao DW, Sun XG, Hu P, Dong J and Zhang TC: MRTF-A and STAT3 synergistically promote breast cancer cell migration. Cell Signal. 26:2370–2380. 2014. View Article : Google Scholar : PubMed/NCBI
24	Medjkane S, Perez-Sanchez C, Gaggioli C, Sahai E and Treisman R: Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis. Nat Cell Biol. 11:257–268. 2009. View Article : Google Scholar : PubMed/NCBI
25	Roth W, Kumar V, Beer HD, Richter M, Wohlenberg C, Reuter U, Thiering S, Staratschek-Jox A, Hofmann A, Kreusch F, et al: Keratin 1 maintains skin integrity and participates in an inflammatory network in skin through interleukin-18. J Cell Sci. 125:5269–5279. 2012. View Article : Google Scholar : PubMed/NCBI
26	Dandapani SV, Sugimoto H, Matthews BD, Kolb RJ, Sinha S, Gerszten RE, Zhou J, Ingber DE, Kalluri R and Pollak MR: α-actinin-4 is required for normal podocyte adhesion. J Biol Chem. 282:467–477. 2007. View Article : Google Scholar
27	Grunewald TG and Butt E: The LIM and SH3 domain protein family: Structural proteins or signal transducers or both? Mol Cancer. 7:312008. View Article : Google Scholar : PubMed/NCBI
28	Matsson H, Eason J, Bookwalter CS, Klar J, Gustavsson P, Sunnegårdh J, Enell H, Jonzon A, Vikkula M, Gutierrez I, et al: α-cardiac actin mutations produce atrial septal defects. Hum Mol Genet. 17:256–265. 2008. View Article : Google Scholar
29	Choi CK, Vicente-Manzanares M, Zareno J, Whitmore LA, Mogilner A and Horwitz AR: Actin and α-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nat Cell Biol. 10:1039–1050. 2008. View Article : Google Scholar
30	Dechat T, Adam SA, Taimen P, Shimi T and Goldman RD: Nuclear lamins. Cold Spring Harb Perspect Biol. 2:a0005472010. View Article : Google Scholar : PubMed/NCBI
31	Iyer KV, Pulford S, Mogilner A and Shivashankar GV: Mechanical activation of cells induces chromatin remodeling preceding MKL nuclear transport. Biophys J. 103:1416–1428. 2012. View Article : Google Scholar : PubMed/NCBI
32	Dvorakova M, Nenutil R and Bouchal P: Transgelins, cytoskeletal proteins implicated in different aspects of cancer development. Expert Rev Proteomics. 11:149–165. 2014. View Article : Google Scholar : PubMed/NCBI
33	Yang Z, Chang YJ, Miyamoto H, Ni J, Niu Y, Chen Z, Chen YL, Yao JL, di Sant'Agnese PA and Chang C: Transgelin functions as a suppressor via inhibition of ARA54-enhanced androgen receptor transactivation and prostate cancer cell growth. Mol Endocrinol. 21:343–358. 2007. View Article : Google Scholar
34	Li Q, Shi R, Wang Y and Niu X: TAGLN suppresses proliferation and invasion, and induces apoptosis of colorectal carcinoma cells. Tumour Biol. 34:505–513. 2013. View Article : Google Scholar