Investigation of the proteins associated with epithelial-mesenchymal transition in skin tumors

Investigation of the proteins associated with epithelial-mesenchymal transition in skin tumors

Aim: While epithelial-mesenchymal transition (EMT) is associated with the complex morphogenetic events during embryogenesis, EMT has also been shown to play an important role in the progression of epithelial cancers. There have been few studies examining ZEB1 and SMAD protein expressions in skin tumor tissues in the literature, and there are no studies evaluating GIT1 protein expression. Materials and Methods: Thirty-seven pieces of squamous cell carcinoma(SCC), 34 pieces of basal cell carcinoma(BCC), 11 pieces of actinic keratosis(AK), 9 pieces of in situ SCC(SCCIS) and 7 pieces of normal skin tissue were included in this study. Results: A statistically significant difference was found between the SMAD1, AREB6 and GIT1 H-scores values of the individuals in the five groups. The levels of SMAD1, AREB6 and GIT1 were higher in SCC than in the control group. In binary comparisons, the SMAD1 H-score values of BCC, SCCIS groups were statistically significantly higher than normal skin. GIT1 H-score values of SCC and BCC groups were significantly higher than normal skin. Conclusion: In skin tumors, EMT is an ever-active mechanism. It is thought that this mechanism is highly controlled in SCC, a more aggressive type of cancer, than in BCC. These results suggest that the investigation of genes related to SMAD1, AREB6 and GIT1 may be useful for research into new molecular targets for the treatment and prevention of metastasis in nonmelanotic skin tumors.

___

  • 1. Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 1995;26:678- 90.
  • 2. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2:442-54.
  • 3. Thiery JP, Acloque H, Huang RY, et al. Epithelialmesenchymal transitions in development and disease. Cell 2009;139:871-90.
  • 4. Katalinic A, Kunze U, Schäfer T. Epidemiology of cutaneous melanoma and non-melanoma skin cancer in Schleswig-Holstein, Germany: incidence, clinical subtypes, tumour stages and localization (epidemiology of skin cancer). British J Dermatology 2003;149:1200-6.
  • 5. Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med 2005;353:2262-9.
  • 6. Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 2007;7:415-28.
  • 7. Gambichler T, Skrygan M, Kaczmarczyk J, et al. Increased expression of TGF-beta/Smad proteins in basal cell carcinoma. Eur J Med Res 2007;12:509-14.
  • 8. Lange D, Persson U, Wollina U, et al. Expression of TGF-beta related Smad proteins in human epithelial skin tumors. Int J Oncol 1999;14:1049-105.
  • 9. Toll A, Masferrer E, Hernández-Ruiz M, et al. Epithelial to mesenchymal transition markers are associated with an increased metastatic risk in primary cutaneous squamous cell carcinomas but are attenuated in lymph node metastases. J Dermatol Sci 2013;72:93- 102.
  • 10. Kalluri R, Weinberg RA. Erratum: The basics of epithelial-mesenchymal transition. J Clin Invest 2009;119:1420-8.
  • 11. Zavadil J, Bitzer M, Liang D, et al. Genetic programs of epithelial cell plasticity directed by transforming growth factor-β. Proc Natl Acad Sci 2001;98:6686- 91.
  • 12. Yang Y, He W, He YZ, et al. Downregulation of Smad1/2/3, p-Smad2/3 and Smad4 in seborrheic keratosis, basal cell carcinoma and squamous cell carcinoma. J Clinical Dermatology-Nanjing 2007;36:423.
  • 13. Shao Y, Zhang J, Zhang R, et al. Examination of Smad2 and Smad4 copy-number variations in skin cancers. Clin Transl Oncol 2012;14:138-42.
  • 14. Xu D, Yuan R, Gu H, et al. The effect of ultraviolet radiation on the transforming growth factor beta 1/ Smads pathway and p53 in actinic keratosis and normal skin. Arch Dermatol Res 2013;305:777-86.
  • 15. Browne G, Sayan AE, Tulchinsky E. ZEB proteins link cell motility with cell cycle control and cell survival in cancer. Cell cycle 2010;9:886-91.
  • 16. Peinado H, Portillo F, Cano A. Transcriptional regulation of cadherins during development and carcinogenesis. Int J Dev Biol 2004;48:365-75.
  • 17. Rosivatz E, Becker I, Specht K, et al. Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol 2002;161:1881-91.
  • 18. Pena C, García JM, Silva J, et al. E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations. Hum Mol Genet 2005;14:3361-70.
  • 19. Shen A, Zhang Y, Yang H, et al. Overexpression of ZEB1 relates to metastasis and invasion in osteosarcoma. J Surg Oncol 2012;105:830-4.
  • 20. Maeda G, Chiba T, Okazaki M, et al. Expression of SIP1 in oral squamous cell carcinomas: implications for E-cadherin expression and tumor progression. Int J Oncol 2005;27:1535-41.
  • 21. Chen H, Lu W, Huang C, et al. Prognostic significance of ZEB1 and ZEB2 in digestive cancers: a cohortbased analysis and secondary analysis. Oncotarget 2017;8:31435.
  • 22. Maitah MiY, Ali S, Ahmad A, et al. Up-regulation of sonic hedgehog contributes to TGF-β1-induced epithelial to mesenchymal transition in NSCLC cells. PloS one 2011;6:e16068-e.
  • 23. Von Hoff DD, LoRusso PM, Rudin CM, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009;361:1164-72.
  • 24. Chan S, Huang W, Chang J, et al. MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis. Oncogene 2014;33:4496-507.
  • 25. Wang G, Bai X, Jiang G, et al. GIT1 overexpression promotes epithelial-mesenchymal transition and predicts poor prognosis in hepatocellular carcinoma. Bioengineered 2021;12:30-43.
  • 26. Huang W-C, Chan S-H, Jang T-H, et al. miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma invasion and metastasis. Cancer Res 2014;74:751-64.
Annals of Medical Research-Cover
  • Yayın Aralığı: Aylık
  • Yayıncı: İnönü Üniversitesi Tıp Fakültesi
Sayıdaki Diğer Makaleler

Anterior segment parameters and intraocular pressure changes after phacoemulsification in pseudoexfoliation syndrome

Ali Simsek, Muge Firat

Trends in pediatric central nervous system cancers in Turkey

Halil Can Kucukyildiz

α-Galactosidase levels in irritable bowel syndrome subtypes and quality of life of patients

Handan Ankarali, Tuba Soysal, Fatih Ermis

A down syndrome patient diagnosed with transient myeloproliferative disease after presenting with cutaneous findings

Ufuk Cakir, Cuneyt Tayman, Dilek Gurlek Gokcebay, Burak Ceran, Turan Derme, Mehmet Orhan Erkan, Seda Sahin

Caregiving burdens, depression levels, and related factors of attendants who care physical treatment and rehabilitation patients who applied to Turgut Ozal Medical Center

Gulsen Gunes, Ramazan Cihad Yilmaz

Could the minor autohemotherapy be a complementary therapy for healthcare professionals to prevent COVID-19 infection?

Aydan Orscelik, Murat Parpucu, Ilker Solmaz, Burak Karaaslan, Betul Agiragac

Investigation of the proteins associated with epithelial-mesenchymal transition in skin tumors

Mustafa Emre Ercin, Elif Sanli, Derya Beyza Sayin Kocakap, Fatma Benli Tanrikulu

Evaluation of stroke risk factors and characteristics in the comorbidity of cancer

Nesrin Helvacı Yilmaz, Ozge Arici Duz, Burcu Polat, Asile Seval Aslan

Blood urea nitrogen level in patients with chronic total occlusion predicts long-term mortality independent of estimated glomerular filtration rate and serum creatine level: (9-year follow-up results)

Tuncay Kiris, Ali Gokhan Ozyildiz, Mustafa Cetin, Savas Ozer, Hakan Duman

Sympatho-vagal activity in the mothers of pediatric cancer and non-cancer patients

Sedat Yildiz, Pinar Cakan