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Assessment of the SRC Inhibition Role in the Efficacy of Breast Cancer Radiotherapy

Shabnam Shahrokh, Vahid Mansouri, Zahra Razzaghi




Introduction: Exposure to the artificial light at night (LAN) effect human health and causes several functional modification in body. Obesity, diabetes, and hormonal changes are reported after LAN in humans. Aim of this study is highlighting critical features of gene expression changes in liver of rats which are received autonomic nervous system.

Methods: Up-regulated proteins of irradiated MDA-MB-231 breast cancer cells by a single and fractioned 10 Gray (Gy) 137Cs γ-radiation were analyzed by ptotein-protein interaction (PPI) network analysis by Cytoscape software via STRING database. The network were analyzed by using Network analyzer to characterized the central genes. Action map was mapped for the queried genes and the added neighbors. via CluePedia-STRING ACTIONS-v10.5- 20.11.2017.

Results: The 14 differentially expressed proteins (DEPs) plus 10 neighbors were interacted to construct a network. Among the 14 queried DEPs FN1, CSPG4, LRP1, GSN, RTN4, and CTSD were highlighted as a complex set in analysis.  Analysis revealed that SRC as an added neighbor were activated by the critical DEPs. Activation of the other oncogene as like AKT1 also were determined.

Conclusion: The results indicate that the inhibition of SRC activity or the inhibition of its activators is a useful function of breast cancer RT.



Breast cancer; Cell; Gene; Radiation; Network


Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, et al. Postoperative radiotherapy in highrisk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999;353(9165):1641-8. doi: 10.1016/S0140-6736(98)09201-0.

Miller ED, Fisher JL, Haglund KE, Grecula JC, Xu-Welliver M, Bertino EM, et al. The addition of chemotherapy to

radiation therapy improves survival in elderly patients with stage III non–small cell lung cancer. J Thorac Oncol. 2018;13(3):426-35. doi: 10.1016/j.jtho.2017.11.135.

Kang J, Ning MS, Feng H, Li H, Bahig H, Brooks ED, et al. Predicting 5-Year Progression and Survival Outcomes for Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Ablative Radiotherapy: Development and

Validation of Robust Prognostic Nomograms. Int J Radiat Oncol Biol Phys. 2019. doi: 10.1016/j.ijrobp.2019.09.037.

Bhatia S, Sharma J, Bukkapatnam S, Oweida A, Lennon S, Phan A, et al. Inhibition of EphB4–Ephrin-B2 Signaling

Enhances Response to Cetuximab–Radiation Therapy in Head and Neck Cancers. Clin Cancer Res. 2018;24(18):4539- 50. doi: 10.1158/1078-0432.CCR-18-0327.

Oing C, Tennstedt P, Simon R, Volquardsen J, Borgmann K, Bokemeyer C, et al. BCL2-overexpressing prostate cancer cells rely on PARP1-dependent end-joining and are sensitive to combined PARP inhibitor and radiation therapy. Cancer Lett. 2018;423:60-70. doi: 10.1016/j. canlet.2018.03.007.

Jamet E, Santoni V. Editorial for Special Issue: 2017 Plant Proteomics. Proteomes.2018;6(3):E28. doi: 10.3390/ proteomes6030028.

Coscia F, Lengyel E, Duraiswamy J, Ashcroft B, Bassani- Sternberg M, Wierer M, et al. Multi-level proteomics identifies CT45 as a chemosensitivity mediator and immunotherapy target in ovarian cancer. Cell. 2018;175(1):159-70. doi: 10.1016/j.cell.2018.08.065.

Yanovich G, Agmon H, Harel M, Sonnenblick A. Peretz SRC Inhibition Role in the Breast Cancer Radiotherapy

T, Geiger T. Clinical proteomics of breast cancer reveals a novel layer of breast cancer classification. Cancer Res. 2018;78(20):6001-10. doi: 10.1158/0008-5472.CAN-18-1079.

Tyanova S, Cox J. Perseus: a bioinformatics platform for integrative analysis of proteomics data in cancer research. Methods Mol Biol. 2018;1711:133-48. doi: 10.1007/978-1-4939-7493-1_7.

Zhang B, Horvath S. A general framework for weighted gene co-expression network analysis. Statistical applications in genetics and molecular biology. Stat Appl Genet Mol Biol. 2005;4(1). doi: 10.2202/1544-6115.1128.

Khanin R, Wit E. How scale-free are biological networks. J Comput Biol. 2006;13(3):810-8. doi: 10.1089/cmb.2006.13.810.

Zamanian-Azodi M, Rezaei-Tavirani M, Rahmati-Rad S,Hasanzadeh H, Tavirani MR, Seyyedi SS. Protein-Protein Interaction Network could reveal the relationship between the breast and colon cancer. Gastroenterol Hepatol Bed Bench. 2015;8(3):215-24. doi: 10.22037/ghfbb.v8i3.763.

Rezaei-Tavirani M, Zamanian-Azodi M, Rajabi S, Masoudi-Nejad A, Rostami-Nejad M, Rahmatirad S. Protein Clustering and Interactome Analysis in Parkinson and Alzheimer’s Diseases. Arch Iran Med. 2016;19(2):101-

doi: 0161902/AIM.007.

Safaei A, Tavirani MR, Azodi MZ, Lashay A, Mohammadi SF, Broumand MG, et al. Diabetic retinopathy and laser therapy in rats: A protein-protein interaction network analysis. J Lasers Med Sci. 2017;8(1):S20-S21. doi: 10.15171/


Rostami-Nejad M, Rezaei-Tavirani M, Zadeh-Esmaeel MM, Rezaei-Tavirani S, Akbari Z, Esmaeili S, et al. Assessment of cytokine-mediated signaling pathway dysregulation in arm skin after CO2 laser therapy. J Lasers Med Sci.2019;10(4):257-63. doi: 10.15171/jlms.2019.42.

Kim MH, Jung SY, Ahn J, Hwang SG, Woo HJ, An S, et al. Quantitative proteomic analysis of single or fractionated radiation-induced proteins in human breast cancer MDAMB- 231 cells. Cell Biosci. 2015;5(1):2. doi: 10.1186/2045-


Rezaei-Tavirani M, Rezaei Tavirani M, Akbari Z, Hajimehdipoor H. Prediction of coffee effects in ratswith healthy and NAFLD conditions based on proteinprotein interaction network analysis. Res J Pharmacogn. 2019;6(4):7-15. doi: 10.22127/rjp.2019.93500.

KhalKhal E, Rezaei-Tavirani M, Razzaghi MR, Rezaei- Tavirani S, Zali H, Rostami-Nejad M. The critical role of dysregulation of antioxidant activity and carbohydrate metabolism in celiac disease. Gastroenterol Hepatol Bed Bench. 2019;12(4):340-7. doi: 10.22037/ghfbb.v12i4.1745.

Zamanian-Azodi M, Rezaei-Tavirani M. Investigation of health benefits of cocoa in human colorectal cancer cell line, HT-29 through interactome analysis. Gastroenterol Hepatol Bed Bench. 2019;12(1):67-73. doi: 10.22037/ghfbb.v0i0.1557.

Frame MC. Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta. 2002;1602(2):114-30. doi: 10.1016/s0304-419x(02)00040-9.

Irby RB, Yeatman TJ. Role of Src expression and activation in human cancer. Oncogene. 2000;19(49):5636-42. doi: 10.1038/sj.onc.1203912.

Kim LC, Song L, Haura EB. Src kinases as therapeutic targets for cancer. Nat Rev Clin Oncol. 2009;6(10):587-95.

doi: 10.1038/nrclinonc.2009.129.

Biscardi JS, Ishizawar RC, Silva CM, Parsons SJ. Tyrosine kinase signalling in breast cancer: epidermal growth factor receptor and c-Src interactions in breast cancer. Breast Cancer Res. 2000;2(3):203-10. doi: 10.1186/bcr55.

Liu H, Radisky DC, Nelson CM, Zhang H, Fata JE, Roth RA, et al. Mechanism of Akt1 inhibition of breast cancer cell invasion reveals a protumorigenic role for TSC2. Proc Natl Acad Sci U S A. 2006;103(11):4134-9. doi: 10.1073/pnas.0511342103.

Ju X, Katiyar S, Wang C, Liu M, Jiao X, Li S, et al. Akt1 governs breast cancer progression in vivo. Proc Natl Acad Sci U S A. 2007;104(18):7438-43. doi: 10.1073/pnas.0605874104.

Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37(4):S9-15. doi: 10.1016/s0959-8049(01)00231-3.

Mielnicki LM, Ying AM, Head KL, Asch HL, Asch BB. Epigenetic regulation of gelsolin expression in human

breast cancer cells. Exp Cell Res. 1999;249(1):161-76. doi:10.1006/excr.1999.4461.

DOI: https://doi.org/10.22037/jlms.v10i4.27723