NDRG-1: Pankreas Kanserindeki Rolü ve Potansiyel Etki Mekanizmaları

Sinem Raday; Hülya Yılmaz Aydoğan

doi:10.48124/husagbilder.1640760

Derleme

NDRG-1: Pankreas Kanserindeki Rolü ve Potansiyel Etki Mekanizmaları

Yıl 2025, Cilt: 8 Sayı: 2, 1 - 18, 28.05.2025

Sinem Raday , Hülya Yılmaz Aydoğan

https://doi.org/10.48124/husagbilder.1640760

Öz

Kötü prognozu nedeniyle kansere bağlı ölümlerin önde gelen nedenlerinden biri olan pankreas kanseri (PK), her iki cinsiyette de en yüksek ölüm/insidans oranına sahiptir. Dünya genelinde ortalama %10’luk beş yıllık genel sağkalım oranı olan PK için 2022 yılında yaklaşık 511.000 yeni vaka ve 467.000 PK-nedenli ölüm bildirilmiştir. Cerrahi rezeksiyon, PK tedavisinde en etkili yöntemdir ancak çoğu hastanın ileri evrede teşhis edilmesi cerrahi tedaviyi kısıtlamaktadır. Standart kemoterapi ajanı olarak kullanılan kemoterapötik ajan Gemsitabin’in etkinliği ise sınırlıdır. Gemsitabine kıyasla daha yüksek sağkalım oranına sahip FOLFIRINOX rejimi ise yüksek toksitite göstermektedir. Dahası kemoterapötik ajanlara direnç gelişimi de tedavi başarısını olumsuz etkilediğinden, günümüzde PK için multidisipliner tedavi yaklaşımları ön plandadır. Tedavideki sınırlılıklar nedeniyle yeni ve hedefe yönelik terapötik stratejilerin geliştirilmesine ihtiyaç vardır. Son çalışmalarda PTEN, SMAD4 ve TP53 gibi tümör baskılayıcılarla etkileşime girerek PI3K/AKT, TGF-β/SMAD4 ve RAS/RAF/MEK/ERK gibi kanserde önemli çeşitli sinyal yollarını düzenlenmesinde etki gösteren N-myc downregüle gen 1 (NDRG1)’in pankreas kanseri dahil birçok agresif solid tümörde anti-onkojenik ve anti-metastatik aktiviteler gösterdiği tespit edilmiştir. Ayrıca hem çoklu onkojenik sinyal yolaklarını inhibe ederek hem de tümör baskılayıcı genlerle etkileşimleri nedeniyle NDRG1'in tümör oluşumunda baskılayıcı bir rol oynayabileceği önerilmektedir. Bu derleme NDRG1’in tümör baskılayıcı genler ile etkileşimini ve sinyal yolaklarının düzenlenmesindeki fonksiyonlarının PK gelişimindeki etkilerini güncel literatüre dayanarak açıklamaktadır.

Anahtar Kelimeler

NDRG-1, PTEN, p53, SMAD4, pankreas kanseri

Etik Beyan

Yoktur.

Destekleyen Kurum

Yoktur.

Proje Numarası

Yoktur

Teşekkür

Yazarlar İstanbul Üniversitesi Sağlık Bilimleri Enstitüsü'ne teşekkür ederler.

Kaynakça

1.Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63.
2. Dumlu EG, Karakoc D, Ozdemir A. Nonfunctional Pancreatic Neuroendocrine Tumors: Advances in Diagnosis, Management, and Controversies. Int Surg. 2015;100(6):1089-97.
3. Wood LD, Canto MI, Jaffee EM, Simeone DM. Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment. Gastroenterology. 2022;163(2):386-402.e1.
4. Natu J, Nagaraju GP. Gemcitabine effects on tumor microenvironment of pancreatic ductal adenocarcinoma: Special focus on resistance mechanisms and metronomic therapies. Cancer Lett. 2023;573:216382.
5. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-25.
6. Bae DH, Jansson PJ, Huang ML, Kovacevic Z, Kalinowski D, Lee CS, et al. The role of NDRG1 in the pathology and potential treatment of human cancers. J Clin Pathol. 2013;66(11):911-7.
7. Ghafouri-Fard S, Ahmadi Teshnizi S, Hussen BM, Taheri M, Sharifi G. A review on the role of NDRG1 in different cancers. Mol Biol Rep. 2023;50(7):6251-64.
8. Mustonen V, Muruganandam G, Loris R, Kursula P, Ruskamo S. Crystal and solution structure of NDRG1, a membrane-binding protein linked to myelination and tumour suppression. FEBS J. 2021;288(11):3507-29.
9. Murray JT, Campbell DG, Morrice N, Auld GC, Shpiro N, Marquez R, et al. Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. Biochemical Journal. 2004;384(3):477-88.
10. Park KC, Menezes SV, Kalinowski DS, Sahni S, Jansson PJ, Kovacevic Z, et al. Identification of differential phosphorylation and sub-cellular localization of the metastasis suppressor, NDRG1. Biochim Biophys Acta Mol Basis Dis. 2018;1864(8):2644-63.
11. Murakami Y, Hosoi F, Izumi H, Maruyama Y, Ureshino H, Watari K, et al. Identification of sites subjected to serine/threonine phosphorylation by SGK1 affecting N-myc downstream-regulated gene 1 (NDRG1)/Cap43-dependent suppression of angiogenic CXC chemokine expression in human pancreatic cancer cells. Biochemical and biophysical research communications. 2010;396(2):376-81.
12. Zhang J, Chen S, Zhang W, Zhang J, Liu X, Shi H, et al. Human differentiation-related gene NDRG1 is a Myc downstream-regulated gene that is repressed by Myc on the core promoter region. Gene. 2008;417(1-2):5-12. 13. Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J, et al. Genomic targets of the human c-Myc protein. Genes Dev. 2003;17(9):1115-29.
14. Han LL, Hou L, Zhou MJ, Ma ZL, Lin DL, Wu L, et al. Aberrant NDRG1 methylation associated with its decreased expression and clinicopathological significance in breast cancer. J Biomed Sci. 2013;20(1):52.
15. Chang X, Zhang S, Ma J, Li Z, Zhi Y, Chen J, et al. Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens. Cell Biochem Biophys. 2013;66(1):93-101. 16. Li Q, Chen H. Transcriptional silencing of N-Myc downstream-regulated gene 1 (NDRG1) in metastatic colon cancer cell line SW620. Clin Exp Metastasis. 2011;28(2):127-35.
17. Angst E, Dawson DW, Nguyen A, Park J, Go VL, Reber HA, et al. Epigenetic regulation affects N-myc downstream-regulated gene 1 expression indirectly in pancreatic cancer cells. Pancreas. 2010;39(5):675-9.
18. Kovacevic Z, Chikhani S, Lui GY, Sivagurunathan S, Richardson DR. The iron-regulated metastasis suppressor NDRG1 targets NEDD4L, PTEN, and SMAD4 and inhibits the PI3K and Ras signaling pathways. Antioxid Redox Signal. 2013;18(8):874-87.
19. Carnero A, Blanco-Aparicio C, Renner O, Link W, Leal JF. The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets. 2008;8(3):187-98.
20. Bandyopadhyay S, Pai SK, Hirota S, Hosobe S, Tsukada T, Miura K, et al. PTEN up-regulates the tumor metastasis suppressor gene Drg-1 in prostate and breast cancer. Cancer research. 2004;64(21):7655-60. 21. Unoki M, Nakamura Y. Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Oncogene. 2001;20(33):4457-65.
22. Kovacevic Z, Chikhani S, Lui GY, Sivagurunathan S, Richardson DR. The iron-regulated metastasis suppressor NDRG1 targets NEDD4L, PTEN, and SMAD4 and inhibits the PI3K and Ras signaling pathways. Antioxidants & redox signaling. 2013;18(8):874-87.
23. Pearce LR, Sommer EM, Sakamoto K, Wullschleger S, Alessi DR. Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney. Biochemical Journal. 2011;436(1):169-79.
24. Sun J, Zhang D, Bae D-H, Sahni S, Jansson P, Zheng Y, et al. Metastasis suppressor, NDRG1, mediates its activity through signaling pathways and molecular motors. Carcinogenesis. 2013;34(9):1943-54.
25. Mello SS, Flowers BM, Mazur PK, Lee JJ, Muller F, Denny SK, et al. Multifaceted role for p53 in pancreatic cancer suppression. Proc Natl Acad Sci U S A. 2023;120(10):e2211937120.
26. Liu Y, Su Z, Tavana O, Gu W. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell. 2024;42(6):946-67.
27. Luo J. KRAS mutation in pancreatic cancer. Semin Oncol. 2021;48(1):10-8.
28. McCubrey JA, Yang LV, Abrams SL, Steelman LS, Follo MY, Cocco L, et al. Effects of TP53 Mutations and miRs on Immune Responses in the Tumor Microenvironment Important in Pancreatic Cancer Progression. Cells. 2022;11(14):2155.
29. Fiorini C, Cordani M, Padroni C, Blandino G, Di Agostino S, Donadelli M. Mutant p53 stimulates chemoresistance of pancreatic adenocarcinoma cells to gemcitabine. Biochim Biophys Acta. 2015;1853(1):89-100.
30. Morton JP, Timpson P, Karim SA, Ridgway RA, Athineos D, Doyle B, et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci U S A. 2010;107(1):246-51.
31. Stein S, Thomas EK, Herzog B, Westfall MD, Rocheleau JV, Jackson RS, et al. NDRG1 is necessary for p53-dependent apoptosis. Journal of Biological Chemistry. 2004;279(47):48930-40.
32. Croessmann S, Wong HY, Zabransky DJ, Chu D, Mendonca J, Sharma A, et al. NDRG1 links p53 with proliferation-mediated centrosome homeostasis and genome stability. Proceedings of the National Academy of Sciences. 2015;112(37):11583-8.
33. Hata A, Chen Y-G. TGF-β signaling from receptors to Smads. Cold Spring Harbor perspectives in biology. 2016;8(9):a022061.
34. Zhao M, Mishra L, Deng CX. The role of TGF-beta/SMAD4 signaling in cancer. Int J Biol Sci. 2018;14(2):111-23.
35. Xia X, Wu W, Huang C, Cen G, Jiang T, Cao J, et al. SMAD4 and its role in pancreatic cancer. Tumour Biol. 2015;36(1):111-9.
36. Tascilar M, Skinner HG, Rosty C, Sohn T, Wilentz RE, Offerhaus GJ, et al. The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res. 2001;7(12):4115-21.
37. Moore PS, Sipos B, Orlandini S, Sorio C, Real FX, Lemoine NR, et al. Genetic profile of 22 pancreatic carcinoma cell lines. Analysis of K-ras, p53, p16 and DPC4/Smad4. Virchows Arch. 2001;439(6):798-802.
38. Liang C, Xu J, Meng Q, Zhang B, Liu J, Hua J, et al. TGFB1-induced autophagy affects the pattern of pancreatic cancer progression in distinct ways depending on SMAD4 status. Autophagy. 2020;16(3):486-500.
39. Chen Z, Zhang D, Yue F, Zheng M, Kovacevic Z, Richardson DR. The iron chelators Dp44mT and DFO inhibit TGF-beta-induced epithelial-mesenchymal transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1). J Biol Chem. 2012;287(21):17016-28.
40. Whitnall M, Howard J, Ponka P, Richardson DR. A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics. Proceedings of the National Academy of Sciences. 2006;103(40):14901-6.
41. Kovacevic Z, Menezes SV, Sahni S, Kalinowski DS, Bae DH, Lane DJ, et al. The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways. J Biol Chem. 2016;291(3):1029-52.
42. Gholam Azad M, Hussaini M, Russell TM, Richardson V, Kaya B, Dharmasivam M, et al. Multi-modal mechanisms of the metastasis suppressor, NDRG1: Inhibition of WNT/β-catenin signaling by stabilization of protein kinase Cα. J Biol Chem. 2024;300(7):107417.
43. Yuan J, Lovejoy DB, Richardson DR. Novel di-2-pyridyl–derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment. Blood. 2004;104(5):1450-8.
44. Sahni S, Bae D-H, Lane DJ, Kovacevic Z, Kalinowski DS, Jansson PJ, et al. The metastasis suppressor, N-myc downstream-regulated gene 1 (NDRG1), inhibits stress-induced autophagy in cancer cells. Journal of Biological Chemistry. 2014;289(14):9692-709.

NDRG-1: Role and Potential Mechanisms of Action in Pancreatic Cancer

Yıl 2025, Cilt: 8 Sayı: 2, 1 - 18, 28.05.2025

Sinem Raday , Hülya Yılmaz Aydoğan

https://doi.org/10.48124/husagbilder.1640760

Öz

Pancreatic cancer (PC) is a leading cause of cancer-related mortality due to its poor prognosis, and it has the highest mortality/incidence rate in both sexes. In 2022, approximately 511,000 new cases and 467,000 PC-caused deaths were reported worldwide, with an average five-year overall survival rate of 10%. Surgical resection is the most effective treatment modality for PC; however, most patients are diagnosed at an advanced stage, which limits the efficacy of surgical intervention. The chemotherapeutic agent Gemcitabine, which is used as the standard chemotherapy agent, is only marginally effective. The FOLFIRINOX regimen, which has a higher survival rate compared to gemcitabine, exhibits high toxicity. The development of resistance to chemotherapeutic agents also negatively impacts the success of treatment, emphasising the need for multidisciplinary treatment approaches for PC. In recent studies, N-myc downregulated gene 1 (NDRG1), which interacts with tumour suppressors such as PTEN, SMAD4 and TP53 and regulates various important signalling pathways in cancer such as PI3K/AKT, TGF-β/SMAD4 and RAS/RAF/MEK/ERK, has been found to show anti-oncogenic and anti-metastatic activities in many aggressive solid tumours including pancreatic cancer. It is also suggested that NDRG1 may play a suppressive role in tumourigenesis by inhibiting multiple oncogenic signalling pathways and interacting with tumour suppressor genes. This review describes interaction of NDRG1 with tumour suppressor genes and the effects of its functions in the regulation of signalling pathways on the development of PC based on the current literature.

Anahtar Kelimeler

NDRG-1, PTEN, p53, SMAD4, Pancreatic cancer

Proje Numarası

Yoktur

Kaynakça

1.Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63.
2. Dumlu EG, Karakoc D, Ozdemir A. Nonfunctional Pancreatic Neuroendocrine Tumors: Advances in Diagnosis, Management, and Controversies. Int Surg. 2015;100(6):1089-97.
3. Wood LD, Canto MI, Jaffee EM, Simeone DM. Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment. Gastroenterology. 2022;163(2):386-402.e1.
4. Natu J, Nagaraju GP. Gemcitabine effects on tumor microenvironment of pancreatic ductal adenocarcinoma: Special focus on resistance mechanisms and metronomic therapies. Cancer Lett. 2023;573:216382.
5. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-25.
6. Bae DH, Jansson PJ, Huang ML, Kovacevic Z, Kalinowski D, Lee CS, et al. The role of NDRG1 in the pathology and potential treatment of human cancers. J Clin Pathol. 2013;66(11):911-7.
7. Ghafouri-Fard S, Ahmadi Teshnizi S, Hussen BM, Taheri M, Sharifi G. A review on the role of NDRG1 in different cancers. Mol Biol Rep. 2023;50(7):6251-64.
8. Mustonen V, Muruganandam G, Loris R, Kursula P, Ruskamo S. Crystal and solution structure of NDRG1, a membrane-binding protein linked to myelination and tumour suppression. FEBS J. 2021;288(11):3507-29.
9. Murray JT, Campbell DG, Morrice N, Auld GC, Shpiro N, Marquez R, et al. Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. Biochemical Journal. 2004;384(3):477-88.
10. Park KC, Menezes SV, Kalinowski DS, Sahni S, Jansson PJ, Kovacevic Z, et al. Identification of differential phosphorylation and sub-cellular localization of the metastasis suppressor, NDRG1. Biochim Biophys Acta Mol Basis Dis. 2018;1864(8):2644-63.
11. Murakami Y, Hosoi F, Izumi H, Maruyama Y, Ureshino H, Watari K, et al. Identification of sites subjected to serine/threonine phosphorylation by SGK1 affecting N-myc downstream-regulated gene 1 (NDRG1)/Cap43-dependent suppression of angiogenic CXC chemokine expression in human pancreatic cancer cells. Biochemical and biophysical research communications. 2010;396(2):376-81.
12. Zhang J, Chen S, Zhang W, Zhang J, Liu X, Shi H, et al. Human differentiation-related gene NDRG1 is a Myc downstream-regulated gene that is repressed by Myc on the core promoter region. Gene. 2008;417(1-2):5-12. 13. Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J, et al. Genomic targets of the human c-Myc protein. Genes Dev. 2003;17(9):1115-29.
14. Han LL, Hou L, Zhou MJ, Ma ZL, Lin DL, Wu L, et al. Aberrant NDRG1 methylation associated with its decreased expression and clinicopathological significance in breast cancer. J Biomed Sci. 2013;20(1):52.
15. Chang X, Zhang S, Ma J, Li Z, Zhi Y, Chen J, et al. Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens. Cell Biochem Biophys. 2013;66(1):93-101. 16. Li Q, Chen H. Transcriptional silencing of N-Myc downstream-regulated gene 1 (NDRG1) in metastatic colon cancer cell line SW620. Clin Exp Metastasis. 2011;28(2):127-35.
17. Angst E, Dawson DW, Nguyen A, Park J, Go VL, Reber HA, et al. Epigenetic regulation affects N-myc downstream-regulated gene 1 expression indirectly in pancreatic cancer cells. Pancreas. 2010;39(5):675-9.
18. Kovacevic Z, Chikhani S, Lui GY, Sivagurunathan S, Richardson DR. The iron-regulated metastasis suppressor NDRG1 targets NEDD4L, PTEN, and SMAD4 and inhibits the PI3K and Ras signaling pathways. Antioxid Redox Signal. 2013;18(8):874-87.
19. Carnero A, Blanco-Aparicio C, Renner O, Link W, Leal JF. The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets. 2008;8(3):187-98.
20. Bandyopadhyay S, Pai SK, Hirota S, Hosobe S, Tsukada T, Miura K, et al. PTEN up-regulates the tumor metastasis suppressor gene Drg-1 in prostate and breast cancer. Cancer research. 2004;64(21):7655-60. 21. Unoki M, Nakamura Y. Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Oncogene. 2001;20(33):4457-65.
22. Kovacevic Z, Chikhani S, Lui GY, Sivagurunathan S, Richardson DR. The iron-regulated metastasis suppressor NDRG1 targets NEDD4L, PTEN, and SMAD4 and inhibits the PI3K and Ras signaling pathways. Antioxidants & redox signaling. 2013;18(8):874-87.
23. Pearce LR, Sommer EM, Sakamoto K, Wullschleger S, Alessi DR. Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney. Biochemical Journal. 2011;436(1):169-79.
24. Sun J, Zhang D, Bae D-H, Sahni S, Jansson P, Zheng Y, et al. Metastasis suppressor, NDRG1, mediates its activity through signaling pathways and molecular motors. Carcinogenesis. 2013;34(9):1943-54.
25. Mello SS, Flowers BM, Mazur PK, Lee JJ, Muller F, Denny SK, et al. Multifaceted role for p53 in pancreatic cancer suppression. Proc Natl Acad Sci U S A. 2023;120(10):e2211937120.
26. Liu Y, Su Z, Tavana O, Gu W. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell. 2024;42(6):946-67.
27. Luo J. KRAS mutation in pancreatic cancer. Semin Oncol. 2021;48(1):10-8.
28. McCubrey JA, Yang LV, Abrams SL, Steelman LS, Follo MY, Cocco L, et al. Effects of TP53 Mutations and miRs on Immune Responses in the Tumor Microenvironment Important in Pancreatic Cancer Progression. Cells. 2022;11(14):2155.
29. Fiorini C, Cordani M, Padroni C, Blandino G, Di Agostino S, Donadelli M. Mutant p53 stimulates chemoresistance of pancreatic adenocarcinoma cells to gemcitabine. Biochim Biophys Acta. 2015;1853(1):89-100.
30. Morton JP, Timpson P, Karim SA, Ridgway RA, Athineos D, Doyle B, et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci U S A. 2010;107(1):246-51.
31. Stein S, Thomas EK, Herzog B, Westfall MD, Rocheleau JV, Jackson RS, et al. NDRG1 is necessary for p53-dependent apoptosis. Journal of Biological Chemistry. 2004;279(47):48930-40.
32. Croessmann S, Wong HY, Zabransky DJ, Chu D, Mendonca J, Sharma A, et al. NDRG1 links p53 with proliferation-mediated centrosome homeostasis and genome stability. Proceedings of the National Academy of Sciences. 2015;112(37):11583-8.
33. Hata A, Chen Y-G. TGF-β signaling from receptors to Smads. Cold Spring Harbor perspectives in biology. 2016;8(9):a022061.
34. Zhao M, Mishra L, Deng CX. The role of TGF-beta/SMAD4 signaling in cancer. Int J Biol Sci. 2018;14(2):111-23.
35. Xia X, Wu W, Huang C, Cen G, Jiang T, Cao J, et al. SMAD4 and its role in pancreatic cancer. Tumour Biol. 2015;36(1):111-9.
36. Tascilar M, Skinner HG, Rosty C, Sohn T, Wilentz RE, Offerhaus GJ, et al. The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res. 2001;7(12):4115-21.
37. Moore PS, Sipos B, Orlandini S, Sorio C, Real FX, Lemoine NR, et al. Genetic profile of 22 pancreatic carcinoma cell lines. Analysis of K-ras, p53, p16 and DPC4/Smad4. Virchows Arch. 2001;439(6):798-802.
38. Liang C, Xu J, Meng Q, Zhang B, Liu J, Hua J, et al. TGFB1-induced autophagy affects the pattern of pancreatic cancer progression in distinct ways depending on SMAD4 status. Autophagy. 2020;16(3):486-500.
39. Chen Z, Zhang D, Yue F, Zheng M, Kovacevic Z, Richardson DR. The iron chelators Dp44mT and DFO inhibit TGF-beta-induced epithelial-mesenchymal transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1). J Biol Chem. 2012;287(21):17016-28.
40. Whitnall M, Howard J, Ponka P, Richardson DR. A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics. Proceedings of the National Academy of Sciences. 2006;103(40):14901-6.
41. Kovacevic Z, Menezes SV, Sahni S, Kalinowski DS, Bae DH, Lane DJ, et al. The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways. J Biol Chem. 2016;291(3):1029-52.
42. Gholam Azad M, Hussaini M, Russell TM, Richardson V, Kaya B, Dharmasivam M, et al. Multi-modal mechanisms of the metastasis suppressor, NDRG1: Inhibition of WNT/β-catenin signaling by stabilization of protein kinase Cα. J Biol Chem. 2024;300(7):107417.
43. Yuan J, Lovejoy DB, Richardson DR. Novel di-2-pyridyl–derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment. Blood. 2004;104(5):1450-8.
44. Sahni S, Bae D-H, Lane DJ, Kovacevic Z, Kalinowski DS, Jansson PJ, et al. The metastasis suppressor, N-myc downstream-regulated gene 1 (NDRG1), inhibits stress-induced autophagy in cancer cells. Journal of Biological Chemistry. 2014;289(14):9692-709.

Toplam 41 adet kaynakça vardır.

Ayrıntılar

Birincil Dil	Türkçe
Konular	Dahili Hastalıklar Hemşireliği
Bölüm	Makaleler
Yazarlar	Sinem Raday 0000-0002-4683-070X Hülya Yılmaz Aydoğan 0000-0002-8837-6664
Proje Numarası	Yoktur
Erken Görünüm Tarihi	27 Mayıs 2025
Yayımlanma Tarihi	28 Mayıs 2025
Gönderilme Tarihi	16 Şubat 2025
Kabul Tarihi	22 Nisan 2025
Yayımlandığı Sayı	Yıl 2025 Cilt: 8 Sayı: 2

Kaynak Göster

Vancouver	Raday S, Yılmaz Aydoğan H. NDRG-1: Pankreas Kanserindeki Rolü ve Potansiyel Etki Mekanizmaları. Haliç Üniversitesi Sağlık Bilimleri Dergisi. 2025;8(2):1-18.

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