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Serum levels of cytoskeleton remodeling proteins and their mRNA expression in tumor tissue of metastatic laryngeal and hypopharyngeal cancers

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Abstract

Actin-binding proteins (ABPs) and various signaling systems are involved in the process of squamous cell carcinoma of the larynx and hypopharynx (SCCLH) metastasis. The clinical significance of these proteins has not yet been determined. We analyzed the relationship between the mRNA levels of cofilin 1 (CFL1), profilin 1 (PFN1), adenylyl cyclase-associated protein 1 (CAP1), SNAI1 and RND3 and SCCLH metastasis. The serum levels of the above ABPs were estimated and the relationship between them and their mRNA expressions was analyzed. The expression levels of ABP mRNAs were measured by real-time RT-PCR in paired tissue samples taken from 54 patients with SCCLH (T1-4N0-1M0). Expression analysis was performed using the 2−ΔΔCT method. The levels of ABPs in the blood serum were measured by ELISA. Statistical analysis was carried out using the SPSS Statistica 20.0 software package. No significant difference in the mRNA gene expression in tumor tissue of patients with T1-3N0M0 SCCLH and patients with T2-4N1-2M0 SCCLH was found. High expression of RND3 mRNA was accompanied by an increase in mRNA expression of all studied ABPs. In the blood serum of T2-4N1-2M0 patients, the level of PFN1 was lower by 21% and the level of CAP1 was higher by 75% than those observed in T1-4N0M0 patients. The data obtained showed that RND3 is involved in the regulation of molecular cascades of SCCLH metastasis. PFN1 and CAP1 serum levels can be good classifiers of metastases in patients with SCCLH.

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References

  1. Lee SC, Tang IP, Avatar SP, Ahmad N, Selva KS, Tay KK, Vikneswaran T, Tan TY (2011) Head and neck cancer: possible causes for delay in diagnosis and treatment. Med J Malays 66(2):101–104

    CAS  Google Scholar 

  2. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Investig 119(6):1420–1428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Santamaria PG, Moreno-Bueno G, Portillo F, Cano A (2017) EMT: Present and future in clinical oncology. Mol Oncol 11(7):718–738

    Article  PubMed  PubMed Central  Google Scholar 

  4. Alexandrova AY (2014) Plasticity of tumor cell migration: acquisition of new properties or return to the past? Biochemistry 79(9):947–963. https://doi.org/10.1134/S0006297914090107

    Article  CAS  PubMed  Google Scholar 

  5. Chikina AS, Alexandrova AY (2018) An in vitro system to study the mesenchymal-to-amoeboid transition. In: Gautreau A (ed) Cell migration. Methods in molecular biology, vol 1749. Humana Press, New York. https://doi.org/10.1007/978-1-4939-7701-7_3

    Chapter  Google Scholar 

  6. Kakurina GV, Kolegova ES, Shashova EE, Cheremisina OV, Choynzonov EL, Kondakova IV (2020) Relationship between the mRNA expression levels of calpains 1/2 and proteins involved in cytoskeleton remodeling. Acta Naturae 12(1):110–113. https://doi.org/10.32607/actanaturae.10947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wu Y, Zhou BP (2010) Snail: more than EMT. Cell Adhes Migr 4(2):199–203

    Article  Google Scholar 

  8. Hidalgo-Carcedo C, Hooper S, Chaudhry ShI, Williamson P, Harrington K, Leitinger B, Sahai E (2011) Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6. Nat Cell Biol 13(1):49–58

    Article  CAS  PubMed  Google Scholar 

  9. Ridley AJ (2015) Rho GTPase signalling in cell migration. Curr Opin Cell Biol 36:103–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jansen S, Gosens R, Wieland T, Schmidt M (2018) Paving the Rho in cancer metastasis: Rho GTPases and beyond. Pharmacol Ther 183:1–21

    Article  CAS  PubMed  Google Scholar 

  11. Liu B, Dong H, Lin X, Yang X, Yue X, Yang J, Li Y, Wu L, Zhu X, Zhang S, Tian D, Wang J, Cai Q, Mao S, Chen Q, Chang J (2016) RND3 promotes Snail1 protein degradation and inhibits glioblastoma cell migration and invasion. Oncotarget 7(50):82411–82423

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kakurina GV, Kondakova IV, Cheremisina OV, Shishkin DA, Choinzonov EL (2016) Adenylyl cyclase-associated protein 1 in the development of head and neck squamous cell carcinomas. Bull Exp Biol Med 160(5):695–697. https://doi.org/10.1007/s10517-016-3252-2

    Article  CAS  PubMed  Google Scholar 

  13. Kakurina GV, Kondakova IV, Spirina LV, Kolegova ES, Shashova EE, Cheremisina OV, Novikov VA, Choinzonov EL (2018) Expression of genes encoding cell motility proteins during progression of head and neck squamous cell carcinoma. Bull Exp Biol Med 166(2):250–252. https://doi.org/10.1007/s10517-018-4325-1

    Article  CAS  PubMed  Google Scholar 

  14. Coumans JVF, Davey RJ, Moens PDJ (2018) Cofilin and profilin: partners in cancer aggressiveness. Biophys Rev 10(5):1323–1335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kondakova IV, Iunusova NV, Spirina LV, Kolomiets LA, Villert AB (2014) Association of intracellular proteinase activities with the content of locomotor proteins in tissues of primary tumors and metastasis in ovarian cancer. Bioorg Khim 40(6):735–742. https://doi.org/10.1134/s1068162014060089

    Article  CAS  PubMed  Google Scholar 

  16. Sun B, Fang Y, Li Z, Chen Z, Xiang J (2015) Role of cellular cytoskeleton in epithelial-mesenchymal transition process during cancer progression. Biomed Rep 3(5):603–610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shishkin S, Eremina L, Pashintseva N, Kovalev L, Kovaleva M (2016) Cofilin-1 and other ADF/cofilin superfamily members in human malignant cells. Int J Mol Sci 18(1):10

    Article  PubMed Central  Google Scholar 

  18. Zhang Y, Liao R, Li H, Liu L, Chen X, Chen H (2015) Expression of cofilin-1 and transgelin in esophageal squamous cell carcinoma. Med Sci Monit 21:2659–2665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hotulainen P, Paunola E, Vartiainen MK, Lappalainen P (2005) Actin-depolymerizing factor and cofilin-1 play overlapping roles in promoting rapid F-actin depolymerization in mammalian nonmuscle cells. Mol Biol Cell 16(2):649–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kakurina GV, Kolegova ES, Kondakova IV (2018) Adenylyl cyclase-associated protein 1: structure, regulation, and participation in cellular processes. Biochemistry 83(1):45–53. https://doi.org/10.1134/S0006297918010066

    Article  CAS  PubMed  Google Scholar 

  21. Li M, Yang X, Shi H, Ren H, Chen X, Zhang S, Zhu J, Zhang J (2013) Downregulated expression of the cyclase-associated protein 1 (CAP1) reduces migration in esophageal squamous cell carcinoma. Jpn J Clin Oncol 43(9):856–864

    Article  PubMed  Google Scholar 

  22. Cao HH, Zhang SY, Shen JH, Wu ZY, Wu JY, Wang SH, Li EM, Xu LY (2015) A three-protein signature and clinical outcome in esophageal squamous cell carcinoma. Oncotarget 6(7):5435–5448

    Article  PubMed  Google Scholar 

  23. Schoppmeyer R, Zhao R, Cheng H, Hamed M, Liu C, Zhou X, Schwarz EC et al (2017) Human profilin 1 is a negative regulator of CTL mediated cell-killing and migration. Eur J Immunol 47(9):1562–1572

    Article  CAS  PubMed  Google Scholar 

  24. Davey RJ, Moens PDJ (2020) Profilin: many facets of a small protein. Biophys Rev 12(4):827–849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Narumiya S, Ishizaki T, Watanabe N (1997) Rho effectors and reorganization of actin cytoskeleton. FEBS Lett 410(1):68–72

    Article  CAS  PubMed  Google Scholar 

  26. Rizwani W, Fasim A, Sharma D, Reddy DJ, Bin Omar NAM, Singh SS (2014) S137 phosphorylation of profilin1 is an important signaling event in breast cancer progression. PLoS ONE 9(8):e103868

    Article  PubMed  PubMed Central  Google Scholar 

  27. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  28. Parodi S, Muselli M, Carlini B, Fontana V, Haupt R, Pistoia V, Corrias MV (2016) Restricted ROC curves are useful tools to evaluate the performance of tumour markers. Stat Methods Med Res 25(1):294–314. https://doi.org/10.1177/0962280212452199

    Article  CAS  PubMed  Google Scholar 

  29. Gould CM, Courtneidge SA (2014) Regulation of invadopodia by the tumor microenvironment. Cell Adhes Migr 8(3):226–235. https://doi.org/10.4161/cam.28346

    Article  Google Scholar 

  30. Kotila T, Wioland H, Gl E et al (2019) Mechanism of synergistic actin filament pointed end depolymerization by cyclase-associated protein and cofilin. Nat Commun 10:5320

    Article  PubMed  PubMed Central  Google Scholar 

  31. Chan AY, Bailly M, Zebda N, Segall JE, Condeelis JS (2000) Role of cofilin in epidermal growth factor-stimulated actin polymerization and lamellipod protrusion. J Cell Biol 148(3):531–542. https://doi.org/10.1083/jcb.148.3.531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xie S, Shen C, Tan M, Li M, Song X, Wang C (2017) Systematic analysis of gene expression alterations and clinical outcomes of adenylate cyclase-associated protein in cancer. Oncotarget 8(16):27216–27239

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hasan R, Zhou G-L (2019) The cytoskeletal protein cyclase-associated protein 1 (CAP1) in breast cancer: context-dependent roles in both the invasiveness and proliferation of cancer cells and underlying cell signals. Int J Mol Sci 20(11):2653. https://doi.org/10.3390/ijms20112653

    Article  CAS  PubMed Central  Google Scholar 

  34. Jie W, Andrade KC, Lin X, Yang X, Yue X, Chang J (2015) Pathophysiological functions of Rnd3/RhoE. Compr Physiol 6(1):169–186

    Article  PubMed  PubMed Central  Google Scholar 

  35. Diamond MI, Cai S, Boudreau A, Carey CJ Jr, Lyle N, Pappu RV, Swamidass SJ, Bissell M, Piwnica-Worms H, Shao J (2015) Subcellular localization and Ser-137 phosphorylation regulate tumor-suppressive activity of profilin-1. J Biol Chem 290(14):9075–9086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lee M-H, Kundu JK, Chae J-I, Shim JH (2019) Targeting ROCK/LIMK/cofilin signaling pathway in cancer. Arch Pharmacal Res 42:481–491

    Article  CAS  Google Scholar 

  37. Hodge RG, Ridley AJ (2016) Regulating Rho GTPases and their regulators. Nat Rev Mol Cell Biol 17:496–510

    Article  CAS  PubMed  Google Scholar 

  38. Paysan L, Piquet L, Saltel F, Moreau V (2016) Rnd3 in cancer: a review of the evidence for tumor promoter or suppressor. Mol Cancer Res 14(11):1033–1044

    Article  CAS  PubMed  Google Scholar 

  39. Jönsson F, Gurniak CB, Fleischer B, Kirfel G, Witke W (2012) Immunological responses and actin dynamics in macrophages are controlled by N-cofilin but are independent from ADF. PLoS ONE 7(4):e36034. https://doi.org/10.1371/journal.pone.0036034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wang JC, Lee JY-J, Christian S, Dang-Lawson M, Pritchard C, Freeman SA, Gold MR (2017) The Rap1–cofilin-1 pathway coordinates actin reorganization and MTOC polarization at the B cell immune synapse. J Cell Sci 130:1094–1109. https://doi.org/10.1242/jcs.191858

    Article  CAS  PubMed  Google Scholar 

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Funding

RFBR (Russian Foundation for Basic Research) grant No 20-015-00151 «Actin-binding proteins of the systemic blood flow: association with tumor, immune cells and fibroblasts in cancer pathology». Competition A. Dates 2020–2021. Registration number AAAA-A20-120011690012-9. These funding sources have no role in the writing of the manuscript or the decision to submit it for publication.

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Authors and Affiliations

  1. Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russian Federation, 634050

    G. V. Kakurina, O. V. Cheremisina, E. E. Sereda, E. S. Kolegova, I. V. Kondakova & E. L. Choinzonov

  2. Laboratory of Tumor Biochemistry, Cancer Research Institute of Tomsk NRMC, 5, Kooperativny Street, Tomsk, Russia, 634050

    G. V. Kakurina

Authors
  1. G. V. Kakurina
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  2. O. V. Cheremisina
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  3. E. E. Sereda
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  4. E. S. Kolegova
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  5. I. V. Kondakova
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  6. E. L. Choinzonov
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [GVK], [OVC], [EES] and [ESK]. The first draft of the manuscript was written by [GVK] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Example: CRediT taxonomy; Conceptualization: [GVK], [ELC], [IVK]; Methodology: [GVK], [ESK]; Formal analysis and investigation: [GVK], [ESK], [EES]; Writing—original draft preparation: [GVK]; Writing—review and editing: [ELC], [IVK]; Funding acquisition: [IVK]; Resources: [OVC]; Supervision: [ELC], [IVK].

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Correspondence to G. V. Kakurina.

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The manipulations were carried out under conditions of voluntary participation and confidentiality in accordance with the Helsinki Declaration of the World Medical Association “Ethical Principles for Conducting Scientific Medical Research with Human Participation” as amended in 2000. The study was allowed by Ethic Committees of Tomsk National Research Medical Center.

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Informed consent was obtained from all individual participants included in the study.

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Kakurina, G.V., Cheremisina, O.V., Sereda, E.E. et al. Serum levels of cytoskeleton remodeling proteins and their mRNA expression in tumor tissue of metastatic laryngeal and hypopharyngeal cancers. Mol Biol Rep 48, 5135–5142 (2021). https://doi.org/10.1007/s11033-021-06510-x

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  • DOI: https://doi.org/10.1007/s11033-021-06510-x

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