Kolon Kanserinde Notch Yolağına Duyarlı Gen Ekspresyonlarının Araştırılması
Yıl 2025,
Cilt: 1 Sayı: 1, 1 - 7, 14.07.2025
Asiye Boz Er
,
Zuhal Semiz
,
Ebiha Can
,
Gülsüm Yetkin
,
İdris Er
Öz
Kolorektal kanser (CRC), tedaviye direnç ve metastaz nedeniyle kanserle ilişkili ölümlerin önde gelen nedenlerinden biridir. Bu çalışma, CRC’de Notch sinyal yolunun rolünü araştırarak sağlıklı CCD841-con hücreleri ile HCT116 kolorektal kanser hücreleri arasındaki yolakla ilişkili genlerin ekspresyonlarını karşılaştırmıştır.
Yarı-kantitatif PCR analizi, HCT116 hücrelerinde GATA3 (4 kat), HES (5 kat) ve HEY (3 kat) genlerinin anlamlı şekilde arttığını, buna karşılık PTCRA ekspresyonunun 4 kat azaldığını ortaya koymuştur (p < 0.005, GAPDH’ye normalize edilmiştir). Bu sonuçlar, Notch sinyal yolunun CRC’de tümör progresyonuna katkıda bulunabileceğini göstermektedir. HES ve HEY genlerinin artmış ekspresyonu, epitel-mezenkimal geçiş (EMT) ve kanser kök hücre benzeri özelliklerle ilişkili olabilir.
Genel olarak, bu çalışma Notch yolunun hedeflenmesinin CRC tedavisi için potansiyel bir strateji olabileceğini vurgulamakta ve tümör gelişimi ile direnç mekanizmalarındaki rolüne dair önemli bulgular sunmaktadır.
Proje Numarası
TKB-2024-1706
Kaynakça
-
1. Bao, B., Wang, Z., Ali, S., Kong, D., Li, Y., Ahmad, A., et al. 2011. Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells. Cancer Lett, 307, 26-36.
-
2. Fabregat, I., Malfettone, A. & Soukupova, J. 2016. New Insights into the Crossroads between EMT and Stemness in the Context of Cancer. J Clin Med, 5.
-
3. Hosokawa, H. & Rothenberg, E. V. 2021. How transcription factors drive choice of the T cell fate. Nat Rev Immunol, 21, 162-176.
-
4. Jenner, R. G., Townsend, M. J., Jackson, I., Sun, K., Bouwman, R. D., Young, R. A., et al. 2009. The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes. Proc Natl Acad Sci U S A, 106, 17876-81.
-
5. Kessler, M., Hoffmann, K., Brinkmann, V., Thieck, O., Jackisch, S., Toelle, B., et al. 2015. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nat Commun, 6, 8989.
-
6. Kumar, A., Gautam, V., Sandhu, A., Rawat, K., Sharma, A. & Saha, L. 2023. Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review. World J Gastrointest Surg, 15, 495-519.
-
7. Li, L., Tang, P., Li, S., Qin, X., Yang, H., Wu, C. & Liu, Y. 2017. Notch signaling pathway networks in cancer metastasis: a new target for cancer therapy. Med Oncol, 34, 180.
8. Meurette, O. & Mehlen, P. 2018. Notch Signaling in the Tumor Microenvironment. Cancer Cell, 34, 536-548.
-
9. Miettinen, M., Mccue, P. A., Sarlomo-Rikala, M., Rys, J., Czapiewski, P., Wazny, K., et al. 2014. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol, 38, 13-22.
-
10. Ott, M. M., Helbing, A., Ott, G., Bartek, J., Fischer, L., Durr, A., et al. 1996. bcl-1 rearrangement and cyclin D1 protein expression in mantle cell lymphoma. J Pathol, 179, 238-42.
-
11. Tindemans, I., Serafini, N., Di Santo, J. P. & Hendriks, R. W. 2014. GATA-3 function in innate and adaptive immunity. Immunity, 41, 191-206.
-
12. Tyagi, A., Sharma, A. K. & Damodaran, C. 2020. A Review on Notch Signaling and Colorectal Cancer. Cells, 9.
-
13. Weng, M. T., Tsao, P. N., Lin, H. L., Tung, C. C., Change, M. C., Chang, Y. T., et al. 2015. Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway. PLoS One, 10, e0144322.
-
14. Zhao, Z. L., Ma, S. R., Wang, W. M., Huang, C. F., Yu, G. T., Wu, T. F., et al. 2015. Notch signaling induces epithelial-mesenchymal transition to promote invasion and metastasis in adenoid cystic carcinoma. Am J Transl Res, 7, 162-74.
-
15. Zhdanovskaya, N., Firrincieli, M., Lazzari, S., Pace, E., Scribani Rossi, P., Felli, M. P., et al. 2021. Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives. Cancers (Basel), 13.
Investigation of Notch Pathway Responsive Gene Expressions In Colon Cancer
Yıl 2025,
Cilt: 1 Sayı: 1, 1 - 7, 14.07.2025
Asiye Boz Er
,
Zuhal Semiz
,
Ebiha Can
,
Gülsüm Yetkin
,
İdris Er
Öz
Colorectal cancer (CRC) is a leading cause of cancer-related mortality, largely due to therapy resistance and metastasis. This study explored the role of Notch signaling in CRC by comparing the expression of pathway-associated genes between healthy CCD841-con cells and HCT116 colorectal cancer cells.
Semi-quantitative PCR analysis revealed significant upregulation of GATA3 (4-fold), HES (5-fold), and HEY (3-fold) in HCT116 cells, while PTCRA expression decreased 4-fold (p < 0.005, normalized to GAPDH). These results suggest that Notch signaling contributes to tumor progression in CRC. The elevated expression of HES and HEY may be linked to epithelial-mesenchymal transition (EMT) and cancer stem cell-like traits.
Overall, this study highlights the potential of targeting the Notch pathway in CRC therapy, offering insights into its role in tumor development and resistance mechanisms.
Destekleyen Kurum
Recep Tayyip Erdogan University
Proje Numarası
TKB-2024-1706
Kaynakça
-
1. Bao, B., Wang, Z., Ali, S., Kong, D., Li, Y., Ahmad, A., et al. 2011. Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells. Cancer Lett, 307, 26-36.
-
2. Fabregat, I., Malfettone, A. & Soukupova, J. 2016. New Insights into the Crossroads between EMT and Stemness in the Context of Cancer. J Clin Med, 5.
-
3. Hosokawa, H. & Rothenberg, E. V. 2021. How transcription factors drive choice of the T cell fate. Nat Rev Immunol, 21, 162-176.
-
4. Jenner, R. G., Townsend, M. J., Jackson, I., Sun, K., Bouwman, R. D., Young, R. A., et al. 2009. The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes. Proc Natl Acad Sci U S A, 106, 17876-81.
-
5. Kessler, M., Hoffmann, K., Brinkmann, V., Thieck, O., Jackisch, S., Toelle, B., et al. 2015. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nat Commun, 6, 8989.
-
6. Kumar, A., Gautam, V., Sandhu, A., Rawat, K., Sharma, A. & Saha, L. 2023. Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review. World J Gastrointest Surg, 15, 495-519.
-
7. Li, L., Tang, P., Li, S., Qin, X., Yang, H., Wu, C. & Liu, Y. 2017. Notch signaling pathway networks in cancer metastasis: a new target for cancer therapy. Med Oncol, 34, 180.
8. Meurette, O. & Mehlen, P. 2018. Notch Signaling in the Tumor Microenvironment. Cancer Cell, 34, 536-548.
-
9. Miettinen, M., Mccue, P. A., Sarlomo-Rikala, M., Rys, J., Czapiewski, P., Wazny, K., et al. 2014. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol, 38, 13-22.
-
10. Ott, M. M., Helbing, A., Ott, G., Bartek, J., Fischer, L., Durr, A., et al. 1996. bcl-1 rearrangement and cyclin D1 protein expression in mantle cell lymphoma. J Pathol, 179, 238-42.
-
11. Tindemans, I., Serafini, N., Di Santo, J. P. & Hendriks, R. W. 2014. GATA-3 function in innate and adaptive immunity. Immunity, 41, 191-206.
-
12. Tyagi, A., Sharma, A. K. & Damodaran, C. 2020. A Review on Notch Signaling and Colorectal Cancer. Cells, 9.
-
13. Weng, M. T., Tsao, P. N., Lin, H. L., Tung, C. C., Change, M. C., Chang, Y. T., et al. 2015. Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway. PLoS One, 10, e0144322.
-
14. Zhao, Z. L., Ma, S. R., Wang, W. M., Huang, C. F., Yu, G. T., Wu, T. F., et al. 2015. Notch signaling induces epithelial-mesenchymal transition to promote invasion and metastasis in adenoid cystic carcinoma. Am J Transl Res, 7, 162-74.
-
15. Zhdanovskaya, N., Firrincieli, M., Lazzari, S., Pace, E., Scribani Rossi, P., Felli, M. P., et al. 2021. Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives. Cancers (Basel), 13.