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Evaluation of the Effect of RhoB Inhibition on Epithelial to Mesenchymal Transition Properties in NSCLC A549 Cells

Yıl 2020, Cilt: 10, 17 - 24, 31.12.2020

Öz

Epithelial to mesenchymal transition (EMT) is a naturally occurring process during embryonic development and wound healing that is implicated in cancer progression when aberrantly reactivated. EMT has also been linked to chemotherapy resistance, anti-apoptosis, migration, and invasion of cells. It is thought to endow cancer cells with the ability to self-renew and mesenchymal properties that promote dissemination and metastasis. RhoB, a protein that binds GTP, regulates cellular processes such as cell survival, tumorigenesis, angiogenesis, migration, and metastasis. RhoB down-regulation is correlated to higher degrees of tumor progression and invasiveness. The loss of RhoB during cancer progression is thought to induce EMT by regulating the expression of certain EMT-associated transcription factors. This study aims to investigate the possible relationship between RhoB expression and the EMT characteristics of non-small cell lung cancer cells, such as in vitro migration proprieties. RhoB siRNA or All Stars siRNA negative control was transfected into A549 cells to determine whether RhoB depletion could promote EMT properties. The wound-healing assay was used for evaluating cell migration. The results demonstrate that the knockdown of RhoB promoted the migration ability of A549 cells. The current study may help to better understand the role of RhoB in EMT.

Kaynakça

  • Abraham, R. T. (2001). Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes & development, 15(17), 2177-2196.
  • Acloque, H., Adams, M. S., Fishwick, K., Bronner-Fraser, M., & Nieto, M. A. (2009). Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. The Journal of clinical investigation, 119(6), 1438-1449
  • Adamson, P., Paterson, H. F., & Hall, A. (1992). Intracellular localization of the P21rho proteins. The Journal of cell biology, 119(3), 617-627.
  • Adnane, J., Muro-Cacho, C., Mathews, L., Sebti, S. M., & Munoz-Antonia, T. (2002). Suppression of rho B expression in invasive carcinoma from head and neck cancer patients. Clinical Cancer Research, 8(7), 2225-2232.
  • Angadi, P. V., & Kale, A. D. (2015). Epithelial-mesenchymal transition-A fundamental mechanism in cancer progression: An overview. Indian Journal of Health Sciences and Biomedical Research (KLEU), 8(2), 77.
  • Aroeira, L. S., Aguilera, A., Sánchez-Tomero, J. A., Bajo, M. A., del Peso, G., Jiménez-Heffernan, J. A., ... & López-Cabrera, M. (2007). Epithelial to mesenchymal transition and peritoneal membrane failure in peritoneal dialysis patients: pathologic significance and potential therapeutic interventions. Journal of the American Society of Nephrology, 18(7), 2004-2013.
  • Baldwin, L.A., Hoff, J.T., Lefringhouse, J., Zhang, M., Jia, C., Liu, Z., Erfani, S., Jin, H., Xu, M., She, Q.B. and Van Nagell, J.R. (2014). CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling. Oncotarget, 5(23), p.12203.
  • Bousquet, E., Mazières, J., Privat, M., Rizzati, V., Casanova, A., Ledoux, A., ... & Pradines, A. (2009). Loss of RhoB expression promotes migration and invasion of human bronchial cells via activation of AKT1. Cancer research, 69(15), 6092-6099.
  • Bousquet, E., Calvayrac, O., Mazieres, J., Lajoie-Mazenc, I., Boubekeur, N., Favre, G., & Pradines, A. (2016). RhoB loss induces Rac1-dependent mesenchymal cell invasion in lung cells through PP2A inhibition. Oncogene, 35(14), 1760-1769.
  • Calvayrac, O., Mazières, J., Figarol, S., Marty‐Detraves, C., Raymond‐Letron, I., Bousquet, E., ... & Guibert, N. (2017). The RAS‐related GTP ase RHOB confers resistance to EGFR‐tyrosine kinase inhibitors in non‐small‐cell lung cancer via an AKT‐dependent mechanism. EMBO molecular medicine, 9(2), 238-250.
  • Charras, G., and Sahai, E. (2014). Physical influences of the extracellular environment on cell migration. Nature reviews Molecular cell biology, 15(12), 813-824.
  • Chen, Z., Sun, J., Pradines, A., Favre, G., Adnane, J., & Sebti, S. M. (2000). Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice. Journal of Biological Chemistry, 275(24), 17974-17978.
  • Chen, W., Niu, S., Ma, X., Zhang, P., Gao, Y., Fan, Y., ... & Zhang, Y. (2016). RhoB acts as a tumor suppressor that inhibits malignancy of clear cell renal cell carcinoma. PLoS One, 11(7), e0157599.
  • Christiansen, J. J., & Rajasekaran, A. K. (2006). Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer research, 66(17), 8319-8326.
  • Forget, M. A., Desrosiers, R. R., Del Maestro, R. F., Moumdjian, R., Shedid, D., Berthelet, F., & Béliveau, R. (2002). The expression of rho proteins decreases with human brain tumor progression: potential tumor markers. Clinical & experimental metastasis, 19(1), 9-15.
  • Friedl, P., & Wolf, K. (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nature reviews cancer, 3(5), 362-374.
  • Friedl, P., & Alexander, S. (2011). Cancer invasion and the microenvironment: plasticity and reciprocity. Cell, 147(5), 992-1009.
  • Gao, Y., Fan, X., Li, W., Ping, W., Deng, Y., & Fu, X. (2014). miR-138-5p reverses gefitinib resistance in non-small cell lung cancer cells via negatively regulating G protein-coupled receptor 124. Biochemical and biophysical research communications, 446(1), 179-186.
  • Hay, E. D. (1968). Organization and fine structure of epithelium and mesenchyme in the developing chick embryo. In Epithelial-Mesenchymal Interactions; 18th Hahnemann Symposium, 1968. Williams & Wilkins.
  • Horiuchi, A., Imai, T., Wang, C., Ohira, S., Feng, Y., Nikaido, T., & Konishi, I. (2003). Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma. Laboratory investigation, 83(6), 861-870.
  • Howe, G. A., & Addison, C. L. (2012). RhoB controls endothelial cell morphogenesis in part via negative regulation of RhoA. Vascular cell, 4(1), 1.
  • Jiang, K., Sun, J., Cheng, J., Djeu, J. Y., Wei, S., & Sebti, S. (2004). Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis. Molecular and cellular biology, 24(12), 5565-5576.
  • Kamai, T., Arai, K., Tsujii, T., Honda, M., & Yoshida, K. (2001). Overexpression of RhoA mRNA is associated with advanced stage in testicular germ cell tumour. BJU international, 87(3), 227-231.
  • Kamai, T., Kawakami, S., Koga, F., Arai, G., Takagi, K., Arai, K., ... & Yoshida, K. I. (2003). RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer. BJU international, 91(3), 234-238.
  • Lee, J. M., Dedhar, S., Kalluri, R., & Thompson, E. W. (2006). The epithelial–mesenchymal transition: new insights in signaling, development, and disease. Journal of Cell Biology, 172(7), 973-981.
  • Ma, Q., Gao, Y., Xu, P., Li, K., Xu, X., Gao, J., ... & He, X. (2019). Atorvastatin inhibits breast cancer cells by downregulating PTEN/AKT pathway via promoting ras homolog family member B (RhoB). BioMed research international, 2019.
  • Maier, H. J., Wirth, T., & Beug, H. (2010). Epithelial-mesenchymal transition in pancreatic carcinoma. Cancers, 2(4), 2058-2083.
  • Mayor, R., & Etienne-Manneville, S. (2016). The front and rear of collective cell migration. Nature reviews Molecular cell biology, 17(2), 97.
  • Mazieres, J., Antonia, T., Daste, G., Muro-Cacho, C., Berchery, D., Tillement, V., ... & Favre, G. (2004). Loss of RhoB expression in human lung cancer progression. Clinical cancer research, 10(8), 2742-2750.
  • Mazières, J., Tillement, V., Allal, C., Clanet, C., Bobin, L., Chen, Z., ... & Pradines, A. (2005). Geranylgeranylated, but not farnesylated, RhoB suppresses Ras transformation of NIH-3T3 cells. Experimental cell research, 304(2), 354-364.
  • Micalizzi, D. S., Farabaugh, S. M., & Ford, H. L. (2010). Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. Journal of mammary gland biology and neoplasia, 15(2), 117-134.
  • Molina, J. R., Yang, P., Cassivi, S. D., Schild, S. E., & Adjei, A. A. (2008, May). Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. In Mayo clinic proceedings (Vol. 83, No. 5, pp. 584-594). Elsevier.
  • Padda, S. K., Burt, B. M., Trakul, N., & Wakelee, H. A. (2014, February). Early-stage non-small cell lung cancer: surgery, stereotactic radiosurgery, and individualized adjuvant therapy. In Seminars in oncology (Vol. 41, No. 1, pp. 40-56). WB Saunders.
  • Sato, N., Fukui, T., Taniguchi, T., Yokoyama, T., Kondo, M., Nagasaka, T., ... & Minna, J. D. (2007). RhoB is frequently downregulated in non‐small‐cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line. International journal of cancer, 120(3), 543-551.
  • Shih, J. Y., & Yang, P. C. (2011). The EMT regulator slug and lung carcinogenesis. Carcinogenesis, 32(9), 1299-1304.
  • Skrypek, N., Goossens, S., De Smedt, E., Vandamme, N., & Berx, G. (2017). Epithelial-to-mesenchymal transition: epigenetic reprogramming driving cellular plasticity. Trends in Genetics, 33(12), 943-959.
  • Stone, R. C., Pastar, I., Ojeh, N., Chen, V., Liu, S., Garzon, K. I., & Tomic-Canic, M. (2016). Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell and tissue research, 365(3), 495-506.
  • Te Boekhorst, V., Preziosi, L., & Friedl, P. (2016). Plasticity of cell migration in vivo and in silico. Annual review of cell and developmental biology, 32, 491-526. Thiery, J. P. (2002). Epithelial–mesenchymal transitions in tumour progression. Nature Reviews Cancer, 2(6), 442-454.
  • Thiery, J. P. (2003). Epithelial–mesenchymal transitions in development and pathologies. Current opinion in cell biology, 15(6), 740-746.
  • Thiery, J. P., & Sleeman, J. P. (2006). Complex networks orchestrate epithelial–mesenchymal transitions. Nature reviews Molecular cell biology, 7(2), 131-142.
  • Travis, W. D. (2012). Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas. Modern Pathology, 25(1), S18-S30.
  • Van Helvert, S., Storm, C., & Friedl, P. (2018). Mechanoreciprocity in cell migration. Nature cell biology, 20(1), 8.
  • Vega, F. M., Thomas, M., Reymond, N., & Ridley, A. J. (2015). The Rho GTPase RhoB regulates cadherin expression and epithelial cell-cell interaction. Cell Communication and Signaling, 13(1), 6.
  • Viani, G.A., Boin, A.C., Ikeda, V.Y., Vianna, B.S., Silva, R.S., & Santanella, F. (2012). Thirty years of prophylactic cranial irradiation in patients with small cell lung cancer: a meta-analysis of randomized clinical trials. J Bras Pneumol, 38(3), pp.372-381.
  • Visvader, J. E., & Lindeman, G. J. (2008). Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nature reviews cancer, 8(10), 755-768. Wang, S., Yan-Neale, Y., Fischer, D., Zeremski, M., Cai, R., Zhu, J., ... & Cohen, D. (2003). Histone deacetylase 1 represses the small GTPase RhoB expression in human non-small lung carcinoma cell line. Oncogene, 22(40), 6204-6213.
  • Wang, W., Yi, M., Chen, S., Li, J., Li, G., Yang, J., ... & Li, G. (2016). Significance of the NOR1-FOXA1/HDAC2-Slug regulatory network in epithelial-mesenchymal transition of tumor cells. Oncotarget, 7(13), 16745.
  • World Health Organization. (2018, September 12). Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer.
  • Zhou, J., Li, K., Gu, Y., Feng, B., Ren, G., Zhang, L., ... & Fan, D. (2011). Transcriptional up-regulation of RhoE by hypoxia-inducible factor (HIF)-1 promotes epithelial to mesenchymal transition of gastric cancer cells during hypoxia. Biochemical and biophysical research communications, 415(2), 348-354.
Yıl 2020, Cilt: 10, 17 - 24, 31.12.2020

Öz

Kaynakça

  • Abraham, R. T. (2001). Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes & development, 15(17), 2177-2196.
  • Acloque, H., Adams, M. S., Fishwick, K., Bronner-Fraser, M., & Nieto, M. A. (2009). Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. The Journal of clinical investigation, 119(6), 1438-1449
  • Adamson, P., Paterson, H. F., & Hall, A. (1992). Intracellular localization of the P21rho proteins. The Journal of cell biology, 119(3), 617-627.
  • Adnane, J., Muro-Cacho, C., Mathews, L., Sebti, S. M., & Munoz-Antonia, T. (2002). Suppression of rho B expression in invasive carcinoma from head and neck cancer patients. Clinical Cancer Research, 8(7), 2225-2232.
  • Angadi, P. V., & Kale, A. D. (2015). Epithelial-mesenchymal transition-A fundamental mechanism in cancer progression: An overview. Indian Journal of Health Sciences and Biomedical Research (KLEU), 8(2), 77.
  • Aroeira, L. S., Aguilera, A., Sánchez-Tomero, J. A., Bajo, M. A., del Peso, G., Jiménez-Heffernan, J. A., ... & López-Cabrera, M. (2007). Epithelial to mesenchymal transition and peritoneal membrane failure in peritoneal dialysis patients: pathologic significance and potential therapeutic interventions. Journal of the American Society of Nephrology, 18(7), 2004-2013.
  • Baldwin, L.A., Hoff, J.T., Lefringhouse, J., Zhang, M., Jia, C., Liu, Z., Erfani, S., Jin, H., Xu, M., She, Q.B. and Van Nagell, J.R. (2014). CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling. Oncotarget, 5(23), p.12203.
  • Bousquet, E., Mazières, J., Privat, M., Rizzati, V., Casanova, A., Ledoux, A., ... & Pradines, A. (2009). Loss of RhoB expression promotes migration and invasion of human bronchial cells via activation of AKT1. Cancer research, 69(15), 6092-6099.
  • Bousquet, E., Calvayrac, O., Mazieres, J., Lajoie-Mazenc, I., Boubekeur, N., Favre, G., & Pradines, A. (2016). RhoB loss induces Rac1-dependent mesenchymal cell invasion in lung cells through PP2A inhibition. Oncogene, 35(14), 1760-1769.
  • Calvayrac, O., Mazières, J., Figarol, S., Marty‐Detraves, C., Raymond‐Letron, I., Bousquet, E., ... & Guibert, N. (2017). The RAS‐related GTP ase RHOB confers resistance to EGFR‐tyrosine kinase inhibitors in non‐small‐cell lung cancer via an AKT‐dependent mechanism. EMBO molecular medicine, 9(2), 238-250.
  • Charras, G., and Sahai, E. (2014). Physical influences of the extracellular environment on cell migration. Nature reviews Molecular cell biology, 15(12), 813-824.
  • Chen, Z., Sun, J., Pradines, A., Favre, G., Adnane, J., & Sebti, S. M. (2000). Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice. Journal of Biological Chemistry, 275(24), 17974-17978.
  • Chen, W., Niu, S., Ma, X., Zhang, P., Gao, Y., Fan, Y., ... & Zhang, Y. (2016). RhoB acts as a tumor suppressor that inhibits malignancy of clear cell renal cell carcinoma. PLoS One, 11(7), e0157599.
  • Christiansen, J. J., & Rajasekaran, A. K. (2006). Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer research, 66(17), 8319-8326.
  • Forget, M. A., Desrosiers, R. R., Del Maestro, R. F., Moumdjian, R., Shedid, D., Berthelet, F., & Béliveau, R. (2002). The expression of rho proteins decreases with human brain tumor progression: potential tumor markers. Clinical & experimental metastasis, 19(1), 9-15.
  • Friedl, P., & Wolf, K. (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nature reviews cancer, 3(5), 362-374.
  • Friedl, P., & Alexander, S. (2011). Cancer invasion and the microenvironment: plasticity and reciprocity. Cell, 147(5), 992-1009.
  • Gao, Y., Fan, X., Li, W., Ping, W., Deng, Y., & Fu, X. (2014). miR-138-5p reverses gefitinib resistance in non-small cell lung cancer cells via negatively regulating G protein-coupled receptor 124. Biochemical and biophysical research communications, 446(1), 179-186.
  • Hay, E. D. (1968). Organization and fine structure of epithelium and mesenchyme in the developing chick embryo. In Epithelial-Mesenchymal Interactions; 18th Hahnemann Symposium, 1968. Williams & Wilkins.
  • Horiuchi, A., Imai, T., Wang, C., Ohira, S., Feng, Y., Nikaido, T., & Konishi, I. (2003). Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma. Laboratory investigation, 83(6), 861-870.
  • Howe, G. A., & Addison, C. L. (2012). RhoB controls endothelial cell morphogenesis in part via negative regulation of RhoA. Vascular cell, 4(1), 1.
  • Jiang, K., Sun, J., Cheng, J., Djeu, J. Y., Wei, S., & Sebti, S. (2004). Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis. Molecular and cellular biology, 24(12), 5565-5576.
  • Kamai, T., Arai, K., Tsujii, T., Honda, M., & Yoshida, K. (2001). Overexpression of RhoA mRNA is associated with advanced stage in testicular germ cell tumour. BJU international, 87(3), 227-231.
  • Kamai, T., Kawakami, S., Koga, F., Arai, G., Takagi, K., Arai, K., ... & Yoshida, K. I. (2003). RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer. BJU international, 91(3), 234-238.
  • Lee, J. M., Dedhar, S., Kalluri, R., & Thompson, E. W. (2006). The epithelial–mesenchymal transition: new insights in signaling, development, and disease. Journal of Cell Biology, 172(7), 973-981.
  • Ma, Q., Gao, Y., Xu, P., Li, K., Xu, X., Gao, J., ... & He, X. (2019). Atorvastatin inhibits breast cancer cells by downregulating PTEN/AKT pathway via promoting ras homolog family member B (RhoB). BioMed research international, 2019.
  • Maier, H. J., Wirth, T., & Beug, H. (2010). Epithelial-mesenchymal transition in pancreatic carcinoma. Cancers, 2(4), 2058-2083.
  • Mayor, R., & Etienne-Manneville, S. (2016). The front and rear of collective cell migration. Nature reviews Molecular cell biology, 17(2), 97.
  • Mazieres, J., Antonia, T., Daste, G., Muro-Cacho, C., Berchery, D., Tillement, V., ... & Favre, G. (2004). Loss of RhoB expression in human lung cancer progression. Clinical cancer research, 10(8), 2742-2750.
  • Mazières, J., Tillement, V., Allal, C., Clanet, C., Bobin, L., Chen, Z., ... & Pradines, A. (2005). Geranylgeranylated, but not farnesylated, RhoB suppresses Ras transformation of NIH-3T3 cells. Experimental cell research, 304(2), 354-364.
  • Micalizzi, D. S., Farabaugh, S. M., & Ford, H. L. (2010). Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. Journal of mammary gland biology and neoplasia, 15(2), 117-134.
  • Molina, J. R., Yang, P., Cassivi, S. D., Schild, S. E., & Adjei, A. A. (2008, May). Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. In Mayo clinic proceedings (Vol. 83, No. 5, pp. 584-594). Elsevier.
  • Padda, S. K., Burt, B. M., Trakul, N., & Wakelee, H. A. (2014, February). Early-stage non-small cell lung cancer: surgery, stereotactic radiosurgery, and individualized adjuvant therapy. In Seminars in oncology (Vol. 41, No. 1, pp. 40-56). WB Saunders.
  • Sato, N., Fukui, T., Taniguchi, T., Yokoyama, T., Kondo, M., Nagasaka, T., ... & Minna, J. D. (2007). RhoB is frequently downregulated in non‐small‐cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line. International journal of cancer, 120(3), 543-551.
  • Shih, J. Y., & Yang, P. C. (2011). The EMT regulator slug and lung carcinogenesis. Carcinogenesis, 32(9), 1299-1304.
  • Skrypek, N., Goossens, S., De Smedt, E., Vandamme, N., & Berx, G. (2017). Epithelial-to-mesenchymal transition: epigenetic reprogramming driving cellular plasticity. Trends in Genetics, 33(12), 943-959.
  • Stone, R. C., Pastar, I., Ojeh, N., Chen, V., Liu, S., Garzon, K. I., & Tomic-Canic, M. (2016). Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell and tissue research, 365(3), 495-506.
  • Te Boekhorst, V., Preziosi, L., & Friedl, P. (2016). Plasticity of cell migration in vivo and in silico. Annual review of cell and developmental biology, 32, 491-526. Thiery, J. P. (2002). Epithelial–mesenchymal transitions in tumour progression. Nature Reviews Cancer, 2(6), 442-454.
  • Thiery, J. P. (2003). Epithelial–mesenchymal transitions in development and pathologies. Current opinion in cell biology, 15(6), 740-746.
  • Thiery, J. P., & Sleeman, J. P. (2006). Complex networks orchestrate epithelial–mesenchymal transitions. Nature reviews Molecular cell biology, 7(2), 131-142.
  • Travis, W. D. (2012). Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas. Modern Pathology, 25(1), S18-S30.
  • Van Helvert, S., Storm, C., & Friedl, P. (2018). Mechanoreciprocity in cell migration. Nature cell biology, 20(1), 8.
  • Vega, F. M., Thomas, M., Reymond, N., & Ridley, A. J. (2015). The Rho GTPase RhoB regulates cadherin expression and epithelial cell-cell interaction. Cell Communication and Signaling, 13(1), 6.
  • Viani, G.A., Boin, A.C., Ikeda, V.Y., Vianna, B.S., Silva, R.S., & Santanella, F. (2012). Thirty years of prophylactic cranial irradiation in patients with small cell lung cancer: a meta-analysis of randomized clinical trials. J Bras Pneumol, 38(3), pp.372-381.
  • Visvader, J. E., & Lindeman, G. J. (2008). Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nature reviews cancer, 8(10), 755-768. Wang, S., Yan-Neale, Y., Fischer, D., Zeremski, M., Cai, R., Zhu, J., ... & Cohen, D. (2003). Histone deacetylase 1 represses the small GTPase RhoB expression in human non-small lung carcinoma cell line. Oncogene, 22(40), 6204-6213.
  • Wang, W., Yi, M., Chen, S., Li, J., Li, G., Yang, J., ... & Li, G. (2016). Significance of the NOR1-FOXA1/HDAC2-Slug regulatory network in epithelial-mesenchymal transition of tumor cells. Oncotarget, 7(13), 16745.
  • World Health Organization. (2018, September 12). Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer.
  • Zhou, J., Li, K., Gu, Y., Feng, B., Ren, G., Zhang, L., ... & Fan, D. (2011). Transcriptional up-regulation of RhoE by hypoxia-inducible factor (HIF)-1 promotes epithelial to mesenchymal transition of gastric cancer cells during hypoxia. Biochemical and biophysical research communications, 415(2), 348-354.
Toplam 48 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Mühendislik
Bölüm Makaleler
Yazarlar

Hedayet Yousef

Hiba Khaır

Isık Didem Karagoz

Yayımlanma Tarihi 31 Aralık 2020
Yayımlandığı Sayı Yıl 2020Cilt: 10

Kaynak Göster

APA Yousef, H., Khaır, H., & Karagoz, I. D. (2020). Evaluation of the Effect of RhoB Inhibition on Epithelial to Mesenchymal Transition Properties in NSCLC A549 Cells. The Eurasia Proceedings of Science Technology Engineering and Mathematics, 10, 17-24.