Research Article
BibTex RIS Cite

IRF5 inhibits prostate cancer metastasis and drug resistance by decreasing CXCR4/CXCL12 complex

Year 2021, Volume: 46 Issue: 4, 1632 - 1639, 30.12.2021

Burcin Abas Nesrin Büyükkarıncalı Ozge Cevik

Abstract

Purpose: Prostate cancer is the most common type of cancer in men, and drug resistance is typical in its treatment. Chemokines especially play a role in tumor growth and drug resistance mechanisms. IRF5 is a critical transcription factor in immune response, and its relationship with the chemokine family CXCR4 and CXCL12 was investigated in this study.
Materials and Methods: The pIRF5 plasmid was transfected in an androgen-independent human prostate cancer cell line (PC3), and the IRF5 protein was overexpressed. CXCR4 and CXCL12 protein expression levels were determined by western blot and gene expression levels by the qPCR method. In addition, colony formation was examined in cells after IRF5 transfection, and CXCL12 secretion was measured in cell media.
Results: Cell viability and colony formation were found to be significantly reduced in IRF5 transfected PC3 cells. In addition, CXCR4 and CXCL12 protein expression and gene expression levels of IRF5 transfected cells were found to be significantly decreased.
Conclusion: This study shows that IRF5, a transcription factor, affects CXCR4/CXCL12, which is involved in microenvironment-mediated metastasis developing in prostate cancer. Thus, in the treatment of prostate cancer, IRF5 gene therapy can prevent metastasis and offer essential contributions to newly developed treatment methods in this regard.

Keywords

IRF5 Prostate cancer CXCR4 CXCL12 chemokines

Supporting Institution

Adnan Menderes University Research Grant Projects

Project Number

TPF-19021

Thanks

This work was supported by the Adnan Menderes University Research Grant Projects (TPF-19021) and by a grant (214Z057) from the Scientific and Technological Research Council of Turkey (TUBITAK) to Dr. Ozge Cevik.

References

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018 Nov 1;68(6):394–424.
  • Dubrovska A, Elliott J, Salamone RJ, Telegeev GD, Stakhovsky AE, Schepotin IB, et al. CXCR4 expression in prostate cancer progenitor cells. PLoS One 2012/02/16. 2012;7(2):e31226–e31226.
  • Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 2015 Jan 29;7(5):a016303.
  • Balkwill FR. The chemokine system and cancer. J Pathol 2012 Jan 1;226(2):148–57.
  • Nomiyama H, Hieshima K, Osada N, Kato-Unoki Y, Otsuka-Ono K, Takegawa S, et al. Extensive expansion and diversification of the chemokine gene family in zebrafish: identification of a novel chemokine subfamily CX. BMC Genomics 2008 May 15;9:222.
  • Werner L, Guzner-Gur H, Dotan I. Involvement of CXCR4/CXCR7/CXCL12 Interactions in Inflammatory bowel disease. Theranostics 2013/01/15. 2013;3(1):40–6.
  • Secchiero P, Celeghini C, Cutroneo G, Di Baldassarre A, Rana R, Zauli G. Differential effects of stromal derived factor-1α (SDF-1α) on early and late stages of human megakaryocytic development. Anat Rec 2000 Oct 1;260(2):141–7.
  • Wright LM, Maloney W, Yu X, Kindle L, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts. Bone 2005;36(5):840–53.
  • Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood 2006;107(5):1761–7.
  • Balestrieri ML, Balestrieri A, Mancini FP, Napoli C. Understanding the immunoangiostatic CXC chemokine network. Cardiovasc Res 2008 May 1;78(2):250–6.
  • Vilgelm AE, Richmond A. Chemokines Modulate Immune Surveillance in Tumorigenesis, Metastasis, and Response to Immunotherapy. Front Immunol 2019 Feb 27;10:333.
  • Yin H, Wang Y, Chen W, Zhong S, Liu Z, Zhao J. Drug-resistant CXCR4-positive cells have the molecular characteristics of EMT in NSCLC. Gene 2016;594(1):23–9.
  • Jefferies CA. Regulating IRFs in IFN Driven Disease. Front Immunol [Internet]. 2019 Mar 29;10:325.
  • Li D, De S, Li D, Song S, Matta B, Barnes BJ. Specific detection of interferon regulatory factor 5 (IRF5): A case of antibody inequality. Sci Rep 2016;6(1):31002.
  • Acidereli H, Turut FA, Cevik O. Acetylation of interferon regulatory factor-5 suppresses androgen receptor and downregulates expression of Sox2. Cell Biochem Funct 2021 Mar 29;n/a(n/a).
  • Cevik O, Li D, Baljinnyam E, Manvar D, Pimenta EM, Waris G, et al. Interferon regulatory factor 5 (IRF5) suppresses hepatitis C virus (HCV) replication and HCV-associated hepatocellular carcinoma. J Biol Chem 2017/10/27. 2017 Dec 29;292(52):21676–89.
  • Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 2006;6(9):644–58.
  • Negishi H, Taniguchi T, Yanai H. The Interferon (IFN) Class of Cytokines and the IFN Regulatory Factor (IRF) Transcription Factor Family. Cold Spring Harb Perspect Biol 2018 Nov 1;10(11):a028423.
  • Bi X, Hameed M, Mirani N, Pimenta EM, Anari J, Barnes BJ. Loss of interferon regulatory factor 5 (IRF5) expression in human ductal carcinoma correlates with disease stage and contributes to metastasis. Breast Cancer Res 2011/11/04. 2011;13(6):R111–R111.
  • Yasuda K, Shukla P, Bonegio RG, Rifkin I, Section R. IFN Regulatory Factor-5 Signaling Increases IFN-Gamma Production and Suppresses IL-2 Production from CD4 + T Cells , and Controls IgG Production in B Cells. 2021;4–5.
  • Almuttaqi H, Udalova IA. Advances and challenges in targeting IRF5, a key regulator of inflammation. FEBS J 2018/09/21. 2019 May;286(9):1624–37.
  • Wang X, Guo J, Wang Y, Xiao Y, Wang L, Hua S. Expression Levels of Interferon Regulatory Factor 5 (IRF5) and Related Inflammatory Cytokines Associated with Severity, Prognosis, and Causative Pathogen in Patients with Community-Acquired Pneumonia. Med Sci Monit 2018 May 30;24:3620–30.
  • Chatterjee S, Behnam Azad B, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res 2014;124:31–82.
  • Cojoc M, Peitzsch C, Trautmann F, Polishchuk L, Telegeev GD, Dubrovska A. Emerging targets in cancer management: role of the CXCL12/CXCR4 axis. Onco Targets Ther 2013 Sep 30;6:1347–61.
  • Gatti M, Pattarozzi A, Bajetto A, Würth R, Daga A, Fiaschi P, et al. Inhibition of CXCL12/CXCR4 autocrine/paracrine loop reduces viability of human glioblastoma stem-like cells affecting self-renewal activity. Toxicology 2013;314(2):209–20.
  • Ho TK, Shiwen X, Abraham D, Tsui J, Baker D. Stromal-Cell-Derived Factor-1 (SDF-1)/CXCL12 as Potential Target of Therapeutic Angiogenesis in Critical Leg Ischaemia. Cardiol Res Pract 2012/02/22. 2012;2012:143209.
  • Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001;410(6824):50–6.
  • Ishikawa T, Nakashiro K-I, Klosek K. S, Goda H, Hara S, Uchida D, et al. Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma. Oncol Rep 2009;21(3):707–12.
  • Phillips RJ, Mestas J, Gharaee-Kermani M, Burdick MD, Sica A, Belperio JA, et al. Epidermal Growth Factor and Hypoxia-induced Expression of CXC Chemokine Receptor 4 on Non-small Cell Lung Cancer Cells Is Regulated by the Phosphatidylinositol 3-Kinase/PTEN/AKT/Mammalian Target of Rapamycin Signaling Pathway and Activation of Hypoxia Inducible Factor-1. J Biol Chem 2005 Jun 10;280(23):22473–81.
  • Duda DG, Kozin S V, Kirkpatrick ND, Xu L, Fukumura D, Jain RK. CXCL12 (SDF1α)-CXCR4/CXCR7 Pathway Inhibition: An Emerging Sensitizer for Anticancer Therapies? Clin Cancer Res 2011 Apr 15;17(8):2074 LP – 2080.
  • Teicher BA. Antiangiogenic agents and targets: A perspective. Biochem Pharmacol 2011;81(1):6–12.
  • Adekoya TO, Richardson RM. Cytokines and Chemokines as Mediators of Prostate Cancer Metastasis. Int J Mol Sci 2020 Jun 23;21(12):4449.
  • Zhang X. Interactions between cancer cells and bone microenvironment promote bone metastasis in prostate cancer. Cancer Commun 2019;39(1):76.
  • Lin S-C, Yu-Lee L-Y, Lin S-H. Osteoblastic Factors in Prostate Cancer Bone Metastasis. Curr Osteoporos Rep 2018 Dec;16(6):642–7.
  • Moriuchi M, Moriuchi H, Turner W, Fauci AS. Cloning and analysis of the promoter region of CXCR4, a coreceptor for HIV-1 entry. J Immunol 1997 Nov 1;159(9):4322 LP – 4329.
  • Mamane Y, Heylbroeck C, Génin P, Algarté M, Servant MJ, LePage C, et al. Interferon regulatory factors: the next generation. Gene 1999;237(1):1–14.
  • Cristillo AD, Highbarger HC, Dewar RL, Dimitrov DS, Golding H, Bierer BE. Up-regulation of HIV coreceptor CXCR4 expression in human T lymphocytes is mediated in part by a cAMP-responsive element. FASEB J 2002 Mar 1;16(3):354–64.
  • Ödemis V, Moepps B, Gierschik P, Engele J. Interleukin-6 and cAMP Induce Stromal Cell-derived Factor-1 Chemotaxis in Astroglia by Up-regulating CXCR4 Cell Surface Expression: Implications For Brain Inflammation*. J Biol Chem 2002;277(42):39801–8.
  • Gagliardi MC, De Magistris MT. Maturation of human dendritic cells induced by the adjuvant cholera toxin: role of cAMP on chemokine receptor expression. Vaccine 2003;21(9):856–61.
  • Christian M, Marangos P, Mak I, McVey J, Barker F, White J, et al. Interferon-γ Modulates Prolactin and Tissue Factor Expression in Differentiating Human Endometrial Stromal Cells*. Endocrinology 2001 Jul 1;142(7):3142–51.
  • de Oliveira KB, Guembarovski RL, Guembarovski AMFL, da Silva do Amaral Herrera AC, Sobrinho WJ, Ariza CB, et al. CXCL12, CXCR4 and IFNγ genes expression: implications for proinflammatory microenvironment of breast cancer. Clin Exp Med 2013;13(3):211–9.
  • Katayama A, Ogino T, Bandoh N, Nonaka S, Harabuchi Y. Expression of CXCR4 and Its Down-Regulation by IFN-γ in Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 2005 Apr 15;11(8):2937 LP – 2946.

IRF5, CXCR4/CXCL12 kompleksini azaltarak prostat kanseri metastazını ve ilaç direncini inhibe eder

Year 2021, Volume: 46 Issue: 4, 1632 - 1639, 30.12.2021

Burcin Abas Nesrin Büyükkarıncalı Ozge Cevik

Abstract

Amaç: Prostat kanseri erkeklerde en sık görülen kanser türüdür ve tedavisinde ilaç direnci tipiktir. Kemokinler özellikle tümör büyümesinde ve ilaç direnç mekanizmalarında rol oynarlar. IRF5, immün yanıtta kritik bir transkripsiyon faktörüdür ve bu çalışmada kemokin ailesi CXCR4 ve CXCL12 ile ilişkisi araştırılmıştır.
Gereç ve Yöntem: pIRF5 plazmidi, androjenden bağımsız bir insan prostat kanseri hücre hattında (PC3) transfekte edildi ve IRF5 proteini aşırı eksprese edildi. CXCR4 ve CXCL12 protein ekspresyon seviyeleri western blot ve gen ekspresyon seviyeleri ile qPCR yöntemi ile belirlendi. Ek olarak, IRF5 transfeksiyonundan sonra hücrelerde koloni oluşumu incelendi ve hücre ortamında CXCL12 sekresyonu ölçüldü.
Bulgular: IRF5 ile transfekte edilmiş PC3 hücrelerinde hücre canlılığı ve koloni oluşumunun önemli ölçüde azaldığı bulundu. Ek olarak, IRF5 ile transfekte edilmiş hücrelerin CXCR4 ve CXCL12 protein ekspresyonu ve gen ekspresyon seviyelerinin önemli ölçüde azaldığı tespit edildi.
Sonuç: Bu çalışma, bir transkripsiyon faktörü olan IRF5'in prostat kanserinde gelişen mikroçevre aracılı metastazda yer alan CXCR4/CXCL12'yi etkilediğini göstermektedir. Böylece prostat kanseri tedavisinde IRF5 gen tedavisi metastazı önleyebilir ve bu konuda yeni geliştirilen tedavi yöntemlerine önemli katkılar sunabilir.

Keywords

IRF5 Prostat kanseri CXCR4 CXCL12 kemokinler

Project Number

TPF-19021

References

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018 Nov 1;68(6):394–424.
  • Dubrovska A, Elliott J, Salamone RJ, Telegeev GD, Stakhovsky AE, Schepotin IB, et al. CXCR4 expression in prostate cancer progenitor cells. PLoS One 2012/02/16. 2012;7(2):e31226–e31226.
  • Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 2015 Jan 29;7(5):a016303.
  • Balkwill FR. The chemokine system and cancer. J Pathol 2012 Jan 1;226(2):148–57.
  • Nomiyama H, Hieshima K, Osada N, Kato-Unoki Y, Otsuka-Ono K, Takegawa S, et al. Extensive expansion and diversification of the chemokine gene family in zebrafish: identification of a novel chemokine subfamily CX. BMC Genomics 2008 May 15;9:222.
  • Werner L, Guzner-Gur H, Dotan I. Involvement of CXCR4/CXCR7/CXCL12 Interactions in Inflammatory bowel disease. Theranostics 2013/01/15. 2013;3(1):40–6.
  • Secchiero P, Celeghini C, Cutroneo G, Di Baldassarre A, Rana R, Zauli G. Differential effects of stromal derived factor-1α (SDF-1α) on early and late stages of human megakaryocytic development. Anat Rec 2000 Oct 1;260(2):141–7.
  • Wright LM, Maloney W, Yu X, Kindle L, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts. Bone 2005;36(5):840–53.
  • Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood 2006;107(5):1761–7.
  • Balestrieri ML, Balestrieri A, Mancini FP, Napoli C. Understanding the immunoangiostatic CXC chemokine network. Cardiovasc Res 2008 May 1;78(2):250–6.
  • Vilgelm AE, Richmond A. Chemokines Modulate Immune Surveillance in Tumorigenesis, Metastasis, and Response to Immunotherapy. Front Immunol 2019 Feb 27;10:333.
  • Yin H, Wang Y, Chen W, Zhong S, Liu Z, Zhao J. Drug-resistant CXCR4-positive cells have the molecular characteristics of EMT in NSCLC. Gene 2016;594(1):23–9.
  • Jefferies CA. Regulating IRFs in IFN Driven Disease. Front Immunol [Internet]. 2019 Mar 29;10:325.
  • Li D, De S, Li D, Song S, Matta B, Barnes BJ. Specific detection of interferon regulatory factor 5 (IRF5): A case of antibody inequality. Sci Rep 2016;6(1):31002.
  • Acidereli H, Turut FA, Cevik O. Acetylation of interferon regulatory factor-5 suppresses androgen receptor and downregulates expression of Sox2. Cell Biochem Funct 2021 Mar 29;n/a(n/a).
  • Cevik O, Li D, Baljinnyam E, Manvar D, Pimenta EM, Waris G, et al. Interferon regulatory factor 5 (IRF5) suppresses hepatitis C virus (HCV) replication and HCV-associated hepatocellular carcinoma. J Biol Chem 2017/10/27. 2017 Dec 29;292(52):21676–89.
  • Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 2006;6(9):644–58.
  • Negishi H, Taniguchi T, Yanai H. The Interferon (IFN) Class of Cytokines and the IFN Regulatory Factor (IRF) Transcription Factor Family. Cold Spring Harb Perspect Biol 2018 Nov 1;10(11):a028423.
  • Bi X, Hameed M, Mirani N, Pimenta EM, Anari J, Barnes BJ. Loss of interferon regulatory factor 5 (IRF5) expression in human ductal carcinoma correlates with disease stage and contributes to metastasis. Breast Cancer Res 2011/11/04. 2011;13(6):R111–R111.
  • Yasuda K, Shukla P, Bonegio RG, Rifkin I, Section R. IFN Regulatory Factor-5 Signaling Increases IFN-Gamma Production and Suppresses IL-2 Production from CD4 + T Cells , and Controls IgG Production in B Cells. 2021;4–5.
  • Almuttaqi H, Udalova IA. Advances and challenges in targeting IRF5, a key regulator of inflammation. FEBS J 2018/09/21. 2019 May;286(9):1624–37.
  • Wang X, Guo J, Wang Y, Xiao Y, Wang L, Hua S. Expression Levels of Interferon Regulatory Factor 5 (IRF5) and Related Inflammatory Cytokines Associated with Severity, Prognosis, and Causative Pathogen in Patients with Community-Acquired Pneumonia. Med Sci Monit 2018 May 30;24:3620–30.
  • Chatterjee S, Behnam Azad B, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res 2014;124:31–82.
  • Cojoc M, Peitzsch C, Trautmann F, Polishchuk L, Telegeev GD, Dubrovska A. Emerging targets in cancer management: role of the CXCL12/CXCR4 axis. Onco Targets Ther 2013 Sep 30;6:1347–61.
  • Gatti M, Pattarozzi A, Bajetto A, Würth R, Daga A, Fiaschi P, et al. Inhibition of CXCL12/CXCR4 autocrine/paracrine loop reduces viability of human glioblastoma stem-like cells affecting self-renewal activity. Toxicology 2013;314(2):209–20.
  • Ho TK, Shiwen X, Abraham D, Tsui J, Baker D. Stromal-Cell-Derived Factor-1 (SDF-1)/CXCL12 as Potential Target of Therapeutic Angiogenesis in Critical Leg Ischaemia. Cardiol Res Pract 2012/02/22. 2012;2012:143209.
  • Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001;410(6824):50–6.
  • Ishikawa T, Nakashiro K-I, Klosek K. S, Goda H, Hara S, Uchida D, et al. Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma. Oncol Rep 2009;21(3):707–12.
  • Phillips RJ, Mestas J, Gharaee-Kermani M, Burdick MD, Sica A, Belperio JA, et al. Epidermal Growth Factor and Hypoxia-induced Expression of CXC Chemokine Receptor 4 on Non-small Cell Lung Cancer Cells Is Regulated by the Phosphatidylinositol 3-Kinase/PTEN/AKT/Mammalian Target of Rapamycin Signaling Pathway and Activation of Hypoxia Inducible Factor-1. J Biol Chem 2005 Jun 10;280(23):22473–81.
  • Duda DG, Kozin S V, Kirkpatrick ND, Xu L, Fukumura D, Jain RK. CXCL12 (SDF1α)-CXCR4/CXCR7 Pathway Inhibition: An Emerging Sensitizer for Anticancer Therapies? Clin Cancer Res 2011 Apr 15;17(8):2074 LP – 2080.
  • Teicher BA. Antiangiogenic agents and targets: A perspective. Biochem Pharmacol 2011;81(1):6–12.
  • Adekoya TO, Richardson RM. Cytokines and Chemokines as Mediators of Prostate Cancer Metastasis. Int J Mol Sci 2020 Jun 23;21(12):4449.
  • Zhang X. Interactions between cancer cells and bone microenvironment promote bone metastasis in prostate cancer. Cancer Commun 2019;39(1):76.
  • Lin S-C, Yu-Lee L-Y, Lin S-H. Osteoblastic Factors in Prostate Cancer Bone Metastasis. Curr Osteoporos Rep 2018 Dec;16(6):642–7.
  • Moriuchi M, Moriuchi H, Turner W, Fauci AS. Cloning and analysis of the promoter region of CXCR4, a coreceptor for HIV-1 entry. J Immunol 1997 Nov 1;159(9):4322 LP – 4329.
  • Mamane Y, Heylbroeck C, Génin P, Algarté M, Servant MJ, LePage C, et al. Interferon regulatory factors: the next generation. Gene 1999;237(1):1–14.
  • Cristillo AD, Highbarger HC, Dewar RL, Dimitrov DS, Golding H, Bierer BE. Up-regulation of HIV coreceptor CXCR4 expression in human T lymphocytes is mediated in part by a cAMP-responsive element. FASEB J 2002 Mar 1;16(3):354–64.
  • Ödemis V, Moepps B, Gierschik P, Engele J. Interleukin-6 and cAMP Induce Stromal Cell-derived Factor-1 Chemotaxis in Astroglia by Up-regulating CXCR4 Cell Surface Expression: Implications For Brain Inflammation*. J Biol Chem 2002;277(42):39801–8.
  • Gagliardi MC, De Magistris MT. Maturation of human dendritic cells induced by the adjuvant cholera toxin: role of cAMP on chemokine receptor expression. Vaccine 2003;21(9):856–61.
  • Christian M, Marangos P, Mak I, McVey J, Barker F, White J, et al. Interferon-γ Modulates Prolactin and Tissue Factor Expression in Differentiating Human Endometrial Stromal Cells*. Endocrinology 2001 Jul 1;142(7):3142–51.
  • de Oliveira KB, Guembarovski RL, Guembarovski AMFL, da Silva do Amaral Herrera AC, Sobrinho WJ, Ariza CB, et al. CXCL12, CXCR4 and IFNγ genes expression: implications for proinflammatory microenvironment of breast cancer. Clin Exp Med 2013;13(3):211–9.
  • Katayama A, Ogino T, Bandoh N, Nonaka S, Harabuchi Y. Expression of CXCR4 and Its Down-Regulation by IFN-γ in Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 2005 Apr 15;11(8):2937 LP – 2946.
There are 42 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research
Authors

Burcin Abas This is me 0000-0002-1018-5577

Nesrin Büyükkarıncalı This is me 0000-0003-0422-1225

Ozge Cevik 0000-0002-9325-3757

Project Number TPF-19021
Publication Date December 30, 2021
Acceptance Date October 19, 2021
Published in Issue Year 2021 Volume: 46 Issue: 4

Cite

MLA Abas, Burcin et al. “IRF5 Inhibits Prostate Cancer Metastasis and Drug Resistance by Decreasing CXCR4/CXCL12 Complex”. Cukurova Medical Journal, vol. 46, no. 4, 2021, pp. 1632-9.
Creative Commons Lisansı