FGFR1 SER777 Mutasyonu ve Mesane Kanseri
Yıl 2021,
, 125 - 129, 29.05.2021
Asuman Özgöz
,
Hale Şamlı
,
Murat Şamlı
,
Deniz Dinçel
,
Ümit İnce
,
Ahmet Şahin
Öz
Amaç: ERK 1/2 (ekstraselüler sinyalle düzenlenen kinaz 1, 2) ve p38α’nın, FGFR1 Ser 777’yi fosforile etmek yoluyla anti-tümörojenik etki göstermesi muhtemeldir. Ser777 fosforilasyonunun ise FGFR1 aktivasyonunu inhibe ettiği bilinmektedir. Dolayısıyla Ser777’nin mutasyona uğramasının FGFR1’i aktive ederek; karsinogenez ile bunu devam ettirebilecek mekanizmaları harekete geçirebileceği düşünülmüştür. Bu kapsamda gerçekleştiren çalışmada; mesane kanseri ile FGFR1 Ser777 mutasyonu arasındaki ilişkinin tespiti amaçlanmıştır.
Yöntem: Çalışmada; mesane kanseri tümör dokusu (n=62) ve kontrol grubu örneklerinde (n=30) DNA izolasyonunun ardından, FGFR1 Ser777 mutasyon analizi, DNA dizi analizi yöntemi ile gerçekleştirilmiştir.
Bulgular: Bildiğimiz kadarıyla ilk defa çalışılan söz konusu mutasyon, incelenen hasta ve kontrol grubu örneklerinde tespit edilememiştir.
Sonuç: Elde edilen bulgular, Ser777’nin mesane kanserinde mutasyona uğramadığını düşündürmüştür. Literatürde konuyla ilgili başka çalışma bulunmadığı göz önüne alındığında, çalışma sonuçlarının literatüre önemli katkı sağlayabileceği düşünülmektedir. Dahası, diğer kanser türlerinde de FGRF1 Ser777 mutasyonunun çalışılmasının farklı bakış açıları ortaya koyabileceğini düşünmekteyiz.
Kaynakça
- Andrew AS, Gui J, Hu T et al. Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study. BJUI 2014; 115(2): 238–247. doi: 10.1111/bju.12641. Epub 2014 Mar 26.
- Babaian AIU, Kariakin OB, Teplov AA, Zaletaev DV, Nemtsova MV. Some molecular-genetic markers, defining the pathogenesis of superficial and invasive bladder cancer. Mol. Biol 2011;45(6): 929–932 doi.org/10.1134/S0026893311060021.
- Balbás-Martínez C, Rodríguez-Pinilla M, Casanova A et al. ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors. PloS one, 2013; 8(5), e62483.
- Czerniak B, Dinney C, McConkey D. Origins of Bladder Cancer. Annu Rev Pathol 2016; 11: 149-174. doi:10.1146/annurev-pathol-012513-104703.
- Veri̇m L. Mesane Kanseri Gelişiminde Genetik Değişim ve Hedefler. Deneysel Tıp Araştırma Enstitüsü Dergisi (Experimed) 2016; 5(10): 67-72.
- Felsenstein KM, Theodorescu D. Precision medicine for urothelial bladder cancer: update on tumour genomics and immunotherapy. Nat Rev Urol. 2018;15(2):92-111. doi: 10.1038/nrurol.2017.179.
- Zakrzewska M, Haugsten EM, Nadratowska-Wesolowska B at el. ERK-mediated phosphorylation of fibroblast growth factor receptor 1 on Ser777 inhibits signaling. Sci. Signal 2013; 6(262), ra11. doi.org/10.1126/scisignal.2003087.
- Furdui CM, Lew ED, Schlessinger J, Anderson KS. Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction. Mol Cell 2006; 21(5): 711–717 doi.org/10.1016/j.molcel.2006.01.022.
- Lew ED, Furdui CM, Anderson KS, Schlessinger J. The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations. Sci. Signal 2009; 2(58): ra6 doi.org/10.1126/scisignal.2000021.
- Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth F R., 2005; 16(2): 139–149 doi.org/10.1016/j.cytogfr.2005.01.001.
- N. Turner R. Grose, Fibroblast growth factor signalling: From development to cancer. Nat. Rev. Cancer 2010; 10: 116–129 doi: 10.1038/nrc2780.
- Wesche J, Haglund K, Haugsten EM. Fibroblast growth factors and their receptors in cancer. Biochem. J 2011; 437(2): 199–213 doi.org/10.1042/BJ20101603.
- Lax I, Wong A, Lamothe B et al. The docking protein FRS2alpha controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptors. Mol Cell 2002; 10(4): 709–719 https://doi.org/10.1016/s1097-2765(02)00689-5.
- Cuadrado A, Nebreda AR. Mechanisms and functions of p38 MAPK signalling. Biochem. J 2010; 429(3): 403–417 doi.org/10.1042/BJ20100323.
- Sørensen V, Zhen Y, Zakrzewska M et al. Phosphorylation of fibroblast growth factor (FGF) receptor 1 at Ser777 by p38 mitogen-activated protein kinase regulates translocation of exogenous FGF1 to the cytosol and nucleus. Mol. Cell. Biol 2008; 28(12): 4129–4141 doi.org/10.1128/MCB.02117-07.
- Kostas M, Lampart A, Bober J, Wiedlocha A, Tomala J, Krowarsch D, Otlewski J, Zakrzewska M. Translocation of Exogenous FGF1 and FGF2 Protects the Cell against Apoptosis Independently of Receptor Activation. J Mol Biol. 2018 Oct 19;430(21):4087-4101. doi: 10.1016/j.jmb.2018.08.004.
- Zakrzewska M, Opalinski L, Haugsten EM, Otlewski J, Wiedlocha A. Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling. Int. J. Mol. Sci 2019; 20(8): 1826 doi.org/10.3390/ijms20081826.
- Haugsten EM, Malecki J, Bjørklund SM, Olsnes S, Wesche J. Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis. Mol. Biol. Cell 2008; 19(8): 3390–3403 doi.org/10.1091/mbc.e07-12-1219.
- Fürthauer M, Lin W, Ang SL, Thisse B, Thisse C. Sef is a feedback-induced antagonist of Ras/MAPK-mediated FGF signalling. Nat. Cell Biol 2002; 4(2): 170–174 doi.org/10.1038/ncb750.
- Tsang M, Friesel R, Kudoh T, Dawid IB. Identification of Sef, a novel modulator of FGF signalling. Nat. Cell Biol 2002; 4(2): 165–169. https://doi.org/10.1038/ncb749.
- Cabrita MA, Christofori G. Sprouty proteins, masterminds of receptor tyrosine kinase signaling. Angiogenesis, 2008; 11(1): 53–62 doi.org/10.1007/s10456-008-9089-1.
- Samatar AA, Poulikakos PI. Targeting RAS-ERK signalling in cancer: promises and challenges. Nat. Rev. Drug Discov 2014; 13(12): 928–942 doi.org/10.1038/nrd4281.
- Huth HW, Santos DM, Gravina HD et al. Upregulation of p38 pathway accelerates proliferation and migration of MDA-MB-231 breast cancer cells. Oncol. Rep 2017; 37(4): 2497–2505 doi.org/10.3892/or.2017.5452.
- Wagner EF, Nebreda AR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat. Rev. Cancer 2009; 9(8): 537–549 doi.org/10.1038/nrc2694.
- Cánovas B, Igea A, Sartori AA et al. Targeting p38α Increases DNA Damage, Chromosome Instability, and the Anti-tumoral Response to Taxanes in Breast Cancer Cells. Cancer cell 2018; 33(6): 1094–1110.e8 doi.org/10.1016/j.ccell.2018.04.010.
- Wada M, Canals D, Adada M et al. P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment. Oncogene 2017; 36(47): 6649–6657 doi.org/10.1038/onc.2017.274.
- Greenberg AK, Basu S, Hu J et al. Selective p38 activation in human non-small cell lung cancer. Am J Resp Cell Mol 2002; 26(5): 558–564 doi.org/10.1165/ajrcmb.26.5.4689.
- Leelahavanichkul K, Amornphimoltham P, Molinolo AA, Basile JR, Koontongkaew S, Gutkind JS. A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis. Mol. Oncol 2014; 8(1): 105–118. doi.org/10.1016/j.molonc.2013.10.003.
- Martínez-Limón A, Joaquin M, Caballero M, Posas F, de Nadal, E. The p38 Pathway: From Biology to Cancer Therapy. Int. J. Mol. Sci 2020; 21(6): 1913 doi.org/10.3390/ijms21061913.
FGFR1 SER777 Mutation and Bladder Cancer
Yıl 2021,
, 125 - 129, 29.05.2021
Asuman Özgöz
,
Hale Şamlı
,
Murat Şamlı
,
Deniz Dinçel
,
Ümit İnce
,
Ahmet Şahin
Öz
Objective: The ERK 1/2 (extracellular signal-regulated kinase 1, 2) and p38α probably have an anti-tumorigenic effect by phosphorylating FGFR1 Ser 777. The Ser777 phosphorylation is known to inhibit FGFR1 activation. Therefore, the Ser777 mutation was suggested to trigger the carcinogenesis, and the other continued mechanisms by activating the FGFR were suggested. We aimed to determine the relationship between FGFR1 Ser777 mutation and bladder cancer were aimed to be determined in this context.
Methods: After the DNA isolation of bladder cancer tumor tissues (n = 62) and control group samples (n = 30), the DNA sequence analysis was performed for the FGFR1 Ser777 mutation in the study carried out for this purpose.
Results: The mutation which has been studied for the first time to the best of our knowledge was not detected in the patient and control group samples in the current study.
Conclusion: As a conclusion the data suggested that Ser777 did not mutate in bladder cancer. Considering that there are no other studies on the subject in the literature, it is thought that the results of the study might make a significant contribution to the literature. Moreover, in our opinion, studying the FGRF1 Ser777 mutation in the other types of the cancer will reveal different points of view.
Kaynakça
- Andrew AS, Gui J, Hu T et al. Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study. BJUI 2014; 115(2): 238–247. doi: 10.1111/bju.12641. Epub 2014 Mar 26.
- Babaian AIU, Kariakin OB, Teplov AA, Zaletaev DV, Nemtsova MV. Some molecular-genetic markers, defining the pathogenesis of superficial and invasive bladder cancer. Mol. Biol 2011;45(6): 929–932 doi.org/10.1134/S0026893311060021.
- Balbás-Martínez C, Rodríguez-Pinilla M, Casanova A et al. ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors. PloS one, 2013; 8(5), e62483.
- Czerniak B, Dinney C, McConkey D. Origins of Bladder Cancer. Annu Rev Pathol 2016; 11: 149-174. doi:10.1146/annurev-pathol-012513-104703.
- Veri̇m L. Mesane Kanseri Gelişiminde Genetik Değişim ve Hedefler. Deneysel Tıp Araştırma Enstitüsü Dergisi (Experimed) 2016; 5(10): 67-72.
- Felsenstein KM, Theodorescu D. Precision medicine for urothelial bladder cancer: update on tumour genomics and immunotherapy. Nat Rev Urol. 2018;15(2):92-111. doi: 10.1038/nrurol.2017.179.
- Zakrzewska M, Haugsten EM, Nadratowska-Wesolowska B at el. ERK-mediated phosphorylation of fibroblast growth factor receptor 1 on Ser777 inhibits signaling. Sci. Signal 2013; 6(262), ra11. doi.org/10.1126/scisignal.2003087.
- Furdui CM, Lew ED, Schlessinger J, Anderson KS. Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction. Mol Cell 2006; 21(5): 711–717 doi.org/10.1016/j.molcel.2006.01.022.
- Lew ED, Furdui CM, Anderson KS, Schlessinger J. The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations. Sci. Signal 2009; 2(58): ra6 doi.org/10.1126/scisignal.2000021.
- Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth F R., 2005; 16(2): 139–149 doi.org/10.1016/j.cytogfr.2005.01.001.
- N. Turner R. Grose, Fibroblast growth factor signalling: From development to cancer. Nat. Rev. Cancer 2010; 10: 116–129 doi: 10.1038/nrc2780.
- Wesche J, Haglund K, Haugsten EM. Fibroblast growth factors and their receptors in cancer. Biochem. J 2011; 437(2): 199–213 doi.org/10.1042/BJ20101603.
- Lax I, Wong A, Lamothe B et al. The docking protein FRS2alpha controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptors. Mol Cell 2002; 10(4): 709–719 https://doi.org/10.1016/s1097-2765(02)00689-5.
- Cuadrado A, Nebreda AR. Mechanisms and functions of p38 MAPK signalling. Biochem. J 2010; 429(3): 403–417 doi.org/10.1042/BJ20100323.
- Sørensen V, Zhen Y, Zakrzewska M et al. Phosphorylation of fibroblast growth factor (FGF) receptor 1 at Ser777 by p38 mitogen-activated protein kinase regulates translocation of exogenous FGF1 to the cytosol and nucleus. Mol. Cell. Biol 2008; 28(12): 4129–4141 doi.org/10.1128/MCB.02117-07.
- Kostas M, Lampart A, Bober J, Wiedlocha A, Tomala J, Krowarsch D, Otlewski J, Zakrzewska M. Translocation of Exogenous FGF1 and FGF2 Protects the Cell against Apoptosis Independently of Receptor Activation. J Mol Biol. 2018 Oct 19;430(21):4087-4101. doi: 10.1016/j.jmb.2018.08.004.
- Zakrzewska M, Opalinski L, Haugsten EM, Otlewski J, Wiedlocha A. Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling. Int. J. Mol. Sci 2019; 20(8): 1826 doi.org/10.3390/ijms20081826.
- Haugsten EM, Malecki J, Bjørklund SM, Olsnes S, Wesche J. Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis. Mol. Biol. Cell 2008; 19(8): 3390–3403 doi.org/10.1091/mbc.e07-12-1219.
- Fürthauer M, Lin W, Ang SL, Thisse B, Thisse C. Sef is a feedback-induced antagonist of Ras/MAPK-mediated FGF signalling. Nat. Cell Biol 2002; 4(2): 170–174 doi.org/10.1038/ncb750.
- Tsang M, Friesel R, Kudoh T, Dawid IB. Identification of Sef, a novel modulator of FGF signalling. Nat. Cell Biol 2002; 4(2): 165–169. https://doi.org/10.1038/ncb749.
- Cabrita MA, Christofori G. Sprouty proteins, masterminds of receptor tyrosine kinase signaling. Angiogenesis, 2008; 11(1): 53–62 doi.org/10.1007/s10456-008-9089-1.
- Samatar AA, Poulikakos PI. Targeting RAS-ERK signalling in cancer: promises and challenges. Nat. Rev. Drug Discov 2014; 13(12): 928–942 doi.org/10.1038/nrd4281.
- Huth HW, Santos DM, Gravina HD et al. Upregulation of p38 pathway accelerates proliferation and migration of MDA-MB-231 breast cancer cells. Oncol. Rep 2017; 37(4): 2497–2505 doi.org/10.3892/or.2017.5452.
- Wagner EF, Nebreda AR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat. Rev. Cancer 2009; 9(8): 537–549 doi.org/10.1038/nrc2694.
- Cánovas B, Igea A, Sartori AA et al. Targeting p38α Increases DNA Damage, Chromosome Instability, and the Anti-tumoral Response to Taxanes in Breast Cancer Cells. Cancer cell 2018; 33(6): 1094–1110.e8 doi.org/10.1016/j.ccell.2018.04.010.
- Wada M, Canals D, Adada M et al. P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment. Oncogene 2017; 36(47): 6649–6657 doi.org/10.1038/onc.2017.274.
- Greenberg AK, Basu S, Hu J et al. Selective p38 activation in human non-small cell lung cancer. Am J Resp Cell Mol 2002; 26(5): 558–564 doi.org/10.1165/ajrcmb.26.5.4689.
- Leelahavanichkul K, Amornphimoltham P, Molinolo AA, Basile JR, Koontongkaew S, Gutkind JS. A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis. Mol. Oncol 2014; 8(1): 105–118. doi.org/10.1016/j.molonc.2013.10.003.
- Martínez-Limón A, Joaquin M, Caballero M, Posas F, de Nadal, E. The p38 Pathway: From Biology to Cancer Therapy. Int. J. Mol. Sci 2020; 21(6): 1913 doi.org/10.3390/ijms21061913.