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Translational Therapeutics

PDZK1 confers sensitivity to sunitinib in clear cell renal cell carcinoma by suppressing the PDGFR-β pathway

British Journal of Cancer volume 131, pages 347–360 (2024)Cite this article

Subjects

Abstract

Background

Sunitinib has emerged as the primary treatment for advanced or metastatic clear cell renal cell carcinoma (ccRCC) due to its significant improvement in patients’ average survival time. However, drug resistance and adverse effects of sunitinib pose challenges to its clinical benefits.

Methods

The differentially expressed genes (DEGs) associated with sunitinib sensitivity and resistance in ccRCC were investigated. Cell counting kit-8, plate colony formation, flow cytometry and subcutaneous xenograft tumor model assays were employed to explore the effects of PDZK1 on ccRCC. Further research on the molecular mechanism was conducted through western blot, co-immunoprecipitation, immunofluorescence co-localization and immunohistochemical staining.

Results

We elucidated that PDZK1 is significantly downregulated in sunitinib-resistant ccRCC specimens, and PDZK1 negatively regulates the phosphorylation of PDGFR-β and the activation of its downstream pathways through interaction with PDGFR-β. The dysregulated low levels of PDZK1 contribute to inadequate inhibition of cell proliferation, tumor growth, and insensitivity to sunitinib treatment. Notably, our preclinical investigations showed that miR-15b antagomirs enhance sunitinib cytotoxic effects against ccRCC cells by upregulating PDZK1 levels, suggesting their potential in overcoming sunitinib resistance.

Conclusions

Our findings establish the miR-15b/PDZK1/PDGFR-β axis as a promising therapeutic target and a novel predictor for ccRCC patients’ response to sunitinib treatment.

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Fig. 1: Dysregulated low levels of PDZK1 in sunitinib-resistant ccRCC.
Fig. 2: PDZK1 specifically associates with PDGFR-β via its carboxyl terminus.
Fig. 3: PDZK1 attenuates PDGFR-β-mediated signaling in ccRCC cells.
Fig. 4: PDZK1 retards ccRCC cell proliferation by suppressing PDGFR-β signaling.
Fig. 5: PDZK1 suppresses ccRCC cell proliferation via PDGFR-β signaling in vivo.
Fig. 6: PDZK1 enhances sunitinib sensitivity by downregulating the PDGFR-β signaling pathway.
Fig. 7: High PDZK1 levels are associated with sunitinib sensitivity and attenuation of PDGFR-β signaling in ccRCC specimens.
Fig. 8: hsa-miR-15b-5p inhibitors synergize with sunitinib in inhibiting ccRCC growth.

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Data availability

The previously published data underlying Figs. 1, 2, 7 and Supplementary Figs. 1–6 are openly available in [E-MTAB-3267] at [https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-3267]; [GSE64052] at [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE64052]; [TCGA, Kidney Renal Clear Cell Carcinoma, PanCancer Atlas] at [https://www.cbioportal.org/study/summary?id=kirc_tcga_pan_can_atlas_2018]; [CPTAC, Clear Cell Renal Cell Carcinoma Discovery Cohort] at [https://pdc.cancer.gov/pdc/study/PDC000128]; [GSE210189] at [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE210189]. The data underlying Fig. 5 (tissue microarrays containing 90 pairs of ccRCC and adjacent tissues) and Fig. 7 (23 human ccRCC samples from the First Hospital of Shanxi Medical University) in this study are not publicly available due to patient privacy issues. However, the data are available from the corresponding author upon reasonable request (for research only).

References

  1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48. https://doi.org/10.3322/caac.21763.

    Article  PubMed  Google Scholar 

  2. Capitanio U, Bensalah K, Bex A, Boorjian SA, Bray F, Coleman J, et al. Epidemiology of renal cell carcinoma. Eur Urol. 2019;75:74–84. https://doi.org/10.1016/j.eururo.2018.08.036.

    Article  PubMed  Google Scholar 

  3. Jonasch E, Walker CL, Rathmell WK. Clear cell renal cell carcinoma ontogeny and mechanisms of lethality. Nat Rev Nephrol. 2021;17:245–61. https://doi.org/10.1038/s41581-020-00359-2.

    Article  CAS  PubMed  Google Scholar 

  4. Choueiri TK, Kaelin WG. Targeting the HIF2–VEGF axis in renal cell carcinoma. Nat Med. 2020;26:1519–30. https://doi.org/10.1038/s41591-020-1093-z.

    Article  CAS  PubMed  Google Scholar 

  5. Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev. 2008;34:193–205. https://doi.org/10.1016/j.ctrv.2007.12.001.

    Article  PubMed  Google Scholar 

  6. Kotecha RR, Motzer RJ, Voss MH. Towards individualized therapy for metastatic renal cell carcinoma. Nat Rev Clin Oncol. 2019;16:621–33.

    Article  CAS  PubMed  Google Scholar 

  7. Najjar YG, Rini BI. Novel agents in renal carcinoma: a reality check. Ther Adv Med Oncol. 2012;4:183–94. https://doi.org/10.1177/1758834012443725.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Oudard S, George D, Medioni J, Motzer R. Treatment options in renal cell carcinoma: past, present and future. Ann Oncol. 2007;18:x25–31. https://doi.org/10.1093/annonc/mdm411.

    Article  PubMed  Google Scholar 

  9. Rathmell WK, Rumble RB, Van Veldhuizen PJ, Al-Ahmadie H, Emamekhoo H, Hauke RJ, et al. Management of metastatic clear cell renal cell carcinoma: ASCO guideline. J Clin Oncol. 2022;40:2957–95. https://doi.org/10.1200/JCO.22.00868.

    Article  CAS  PubMed  Google Scholar 

  10. Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, et al. Renal cell carcinoma. Nat Rev Dis Primers. 2017;3. https://doi.org/10.1038/nrdp.2017.9.

  11. Posadas EM, Limvorasak S, Figlin RA. Targeted therapies for renal cell carcinoma. Nat Rev Nephrol. 2017;13:496–511. https://doi.org/10.1038/nrneph.2017.82.

    Article  PubMed  Google Scholar 

  12. Motzer RJ, Rini BI, McDermott DF, Arén Frontera O, Hammers HJ, Carducci MA, et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019;20:1370–85. https://doi.org/10.1016/S1470-2045(19)30413-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Méjean A, Ravaud A, Thezenas S, Chevreau C, Bensalah K, Geoffrois L, et al. Sunitinib alone or after nephrectomy for patients with metastatic renal cell carcinoma: is there still a role for cytoreductive nephrectomy? Eur Urol. 2021;80:417–24. https://doi.org/10.1016/j.eururo.2021.06.009.

    Article  CAS  PubMed  Google Scholar 

  14. Morais C. Sunitinib resistance in renal cell carcinoma. J Kidney Cancer Vhl. 2014;1:1–11.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Dranitsaris G, Schmitz S, Broom RJ. Small molecule targeted therapies for the second-line treatment for metastatic renal cell carcinoma: a systematic review and indirect comparison of safety and efficacy. J Cancer Res Clin Oncol. 2013;139:1917–26. https://doi.org/10.1007/s00432-013-1510-5.

    Article  CAS  PubMed  Google Scholar 

  16. Ravaud A. Treatment-associated adverse event management in the advanced renal cell carcinoma patient treated with targeted therapies. The Oncologist. 2011;16:32–44. https://doi.org/10.1634/theoncologist.2011-S2-32.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bracarda S, Iacovelli R, Boni L, Rizzo M, Derosa L, Rossi M, et al. Sunitinib administered on 2/1 schedule in patients with metastatic renal cell carcinoma: the RAINBOW analysis. Ann Oncol. 2015;26:2107–13. https://doi.org/10.1093/annonc/mdv315.

    Article  CAS  PubMed  Google Scholar 

  18. Bracarda S, Sisani M, Marrocolo F, Hamzaj A, Del Buono S, De Simone V. GOAL: an inverse toxicity-related algorithm for daily clinical practice decision making in advanced kidney cancer. Crit Rev Oncol Hematol. 2014;89:386–93. https://doi.org/10.1016/j.critrevonc.2013.09.002.

    Article  PubMed  Google Scholar 

  19. Knox JJ, Barrios CH, Kim TM, Cosgriff T, Srimuninnimit V, Pittman K, et al. Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC. Ann Oncol. 2017;28:1339–45. https://doi.org/10.1093/annonc/mdx075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yamada Y, Ohno Y, Kato Y, Kobayashi R, Hayashi H, Miyahara S, et al. Optimal dose of sunitinib for long-term treatment in Japanese patients with renal cell carcinoma. Cancer Chemother Pharmacol. 2019;84:987–92. https://doi.org/10.1007/s00280-019-03935-x.

    Article  CAS  PubMed  Google Scholar 

  21. Demlova R, Turjap M, Pes O, Kostolanska K, Jurica J. Therapeutic drug monitoring of sunitinib in gastrointestinal stromal tumors and metastatic renal cell carcinoma in adults—a review. Ther Drug Monit. 2020;42:20–32. https://doi.org/10.1097/FTD.0000000000000663.

    Article  PubMed  Google Scholar 

  22. Jiao Q, Bi L, Ren Y, Song S, Wang Q, Wang Y. Advances in studies of tyrosine kinase inhibitors and their acquired resistance. Mol Cancer. 2018;17. https://doi.org/10.1186/s12943-018-0801-5.

  23. Neul C, Schaeffeler E, Sparreboom A, Laufer S, Schwab M, Nies AT. Impact of membrane drug transporters on resistance to small-molecule tyrosine kinase inhibitors. Trends Pharmacol Sci. 2016;37:904–32. https://doi.org/10.1016/j.tips.2016.08.003.

    Article  CAS  PubMed  Google Scholar 

  24. Westover D, Zugazagoitia J, Cho BC, Lovly CM, Paz-Ares L. Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann Oncol. 2018;29:i10–9. https://doi.org/10.1093/annonc/mdx703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sekino Y, Teishima J, Liang G, Hinata N. Molecular mechanisms of resistance to tyrosine kinase inhibitor in clear cell renal cell carcinoma. Int J Urol. 2022. https://doi.org/10.1111/iju.15042.

  26. Tao T, Yang X, Zheng J, Feng D, Qin Q, Shi X, et al. PDZK1 inhibits the development and progression of renal cell carcinoma by suppression of SHP-1 phosphorylation. Oncogene. 2017;36:6119–31. https://doi.org/10.1038/onc.2017.199.

    Article  CAS  PubMed  Google Scholar 

  27. Zhao C, Tao T, Yang L, Qin Q, Wang Y, Liu H, et al. Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer. Cancer Lett. 2019;453:107–21. https://doi.org/10.1016/j.canlet.2019.03.043.

    Article  CAS  PubMed  Google Scholar 

  28. Wang H, Yang W, Qin Q, Yang X, Yang Y, Liu H, et al. E3 ubiquitin ligase MAGI3 degrades c-Myc and acts as a predictor for chemotherapy response in colorectal cancer. Mol Cancer. 2022;21. https://doi.org/10.1186/s12943-022-01622-9.

  29. Dong LH, Wen JK, Miao SB, Jia Z, Hu HJ, Sun RH, et al. Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRbeta-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia. Cell Res. 2010;20:1252–62. https://doi.org/10.1038/cr.2010.111.

    Article  CAS  PubMed  Google Scholar 

  30. Xue Y, Lim S, Yang Y, Wang Z, Jensen LDE, Hedlund E, et al. PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells. Nat Med. 2012;18:100–10. https://doi.org/10.1038/nm.2575.

    Article  CAS  Google Scholar 

  31. Shim M, Song C, Park S, Choi S, Cho YM, Kim C, et al. Prognostic significance of platelet-derived growth factor receptor-β expression in localized clear cell renal cell carcinoma. J Cancer Res Clin Oncol. 2015;141:2213–20. https://doi.org/10.1007/s00432-015-2019-x.

    Article  CAS  PubMed  Google Scholar 

  32. Carrato Mena A, Grande Pulido E, Guillén-Ponce C. Understanding the molecular-based mechanism of action of the tyrosine kinase inhibitor: sunitinib. Anticancer Drugs. 2010;21:S3–11. https://doi.org/10.1097/01.cad.0000361534.44052.c5.

    Article  CAS  Google Scholar 

  33. Qi Y, Ma Y, Peng Z, Wang L, Li L, Tang Y, et al. Long noncoding RNA PENG upregulates PDZK1 expression by sponging miR-15b to suppress clear cell renal cell carcinoma cell proliferation. Oncogene. 2020;39:4404–20. https://doi.org/10.1038/s41388-020-1297-1.

    Article  CAS  PubMed  Google Scholar 

  34. Lu L, Li Y, Wen H, Feng C. Overexpression of miR-15b promotes resistance to sunitinib in renal cell carcinoma. J Cancer. 2019;10:3389–96. https://doi.org/10.7150/jca.31676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lee WJ, Lee JL, Chang SE, Lee MW, Kang YK, Choi JH, et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol. 2009;161:1045–51. https://doi.org/10.1111/j.1365-2133.2009.09290.x.

    Article  CAS  PubMed  Google Scholar 

  36. Lankhorst S, Baelde HJ, Kappers MHW, Smedts FMM, Hansen A, Clahsen-van Groningen MC, et al. Greater sensitivity of blood pressure than renal toxicity to tyrosine kinase receptor inhibition with sunitinib. Hypertension. 2015;66:543–9. https://doi.org/10.1161/HYPERTENSIONAHA.115.05435.

    Article  CAS  PubMed  Google Scholar 

  37. Narayan V, Keefe S, Haas N, Wang L, Puzanov I, Putt M, et al. Prospective evaluation of sunitinib-induced cardiotoxicity in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2017;23:3601–9. https://doi.org/10.1158/1078-0432.CCR-16-2869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Stitzlein L, Rao P, Dudley R. Emerging oral VEGF inhibitors for the treatment of renal cell carcinoma. Expert Opin Investig Drugs. 2019;28:121–30. https://doi.org/10.1080/13543784.2019.1559296.

    Article  CAS  PubMed  Google Scholar 

  39. Hirsch L, Flippot R, Escudier B, Albiges L. Immunomodulatory roles of VEGF pathway inhibitors in renal cell carcinoma. Drugs. 2020;80:1169–81. https://doi.org/10.1007/s40265-020-01327-7.

    Article  CAS  PubMed  Google Scholar 

  40. Song SH, Jeong IG, You D, Hong JH, Hong B, Song C, et al. VEGF/VEGFR2 and PDGF-B/PDGFR-beta expression in non-metastatic renal cell carcinoma: a retrospective study in 1,091 consecutive patients. Int J Clin Exp Pathol. 2014;7:7681–9.

    PubMed  PubMed Central  Google Scholar 

  41. Baxter RM, Secrist JP, Vaillancourt RR, Kazlauskas A. Full activation of the platelet-derived growth factor beta-receptor kinase involves multiple events. J Biol Chem. 1998;273:17050–5. https://doi.org/10.1074/jbc.273.27.17050.

    Article  CAS  PubMed  Google Scholar 

  42. Kazlauskas A, Durden DL, Cooper JA. Functions of the major tyrosine phosphorylation site of the PDGF receptor β subunit. Cell Regul. 1991;2:413–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nickas ME, Bernard A, Kazlauskas A. The requirement of tyrosines 579 and 581 for maximal ligand-dependent activation of the βPDGFR is influenced by noncytoplasmic regions of the receptor. Exp Cell Res. 2001;265:80–9. https://doi.org/10.1006/excr.2001.5169.

    Article  CAS  PubMed  Google Scholar 

  44. Turner EC, Mulvaney EP, Reid HM, Kinsella BT. Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK1: role in endothelial cell migration and angiogenesis. Mol Biol Cell. 2011;22:2664–79. https://doi.org/10.1091/mbc.E11-04-0374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhu W, Saddar S, Seetharam D, Chambliss KL, Longoria C, Silver DL, et al. The scavenger receptor class B type I adaptor protein PDZK1 maintains endothelial monolayer integrity. Circ Res. 2008;102:480–7. https://doi.org/10.1161/CIRCRESAHA.107.159079.

    Article  CAS  PubMed  Google Scholar 

  46. Dai C, Liang Y, Wang Y, Tiwari AK, Yan Y, Wang F, et al. Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009;279:74–83. https://doi.org/10.1016/j.canlet.2009.01.027.

    Article  CAS  PubMed  Google Scholar 

  47. Shukla S, Robey RW, Bates SE, Ambudkar SV. Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos. 2009;37:359–65. https://doi.org/10.1124/dmd.108.024612.

    Article  CAS  PubMed  Google Scholar 

  48. Jin J, Xie Y, Zhang JS, Wang JQ, Dai SJ, He WF, et al. Sunitinib resistance in renal cell carcinoma: from molecular mechanisms to predictive biomarkers. Drug Resist Updat. 2023;67:100929. https://doi.org/10.1016/j.drup.2023.100929.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Doctor Tongmei Zhang (Beijing Chest Hospital, Capital Medical University) and Doctor Jinwei Miao (Beijing Obstetrics and Gynecology Hospital, Capital Medical University) for kindly providing some clinical samples. We thank Dr. Randy Hall at Emory University (Atlanta, GA) and Dr. Michael R Beard at the Centre for Cancer Biology (Adelaide, Australia) for plasmids materials.

Funding

This study was supported by the National Natural Science Foundation of the People’s Republic of China (Grants Nos. 81772707, 81972732, 82273965); China Postdoctoral Foundation (Grants No. 2023M732409). The funding agency did not participate in the study design, data collection, analysis and interpretation, or the writing of this manuscript.

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Author notes

  1. These authors contributed equally: Haibo Wang, Lijie Zhang.

Authors and Affiliations

  1. Beijing Key Laboratory for Tumor Invasion and Metastasis, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, People’s Republic of China

    Haibo Wang, Hua Liu, Yumeng Yang, Wenxiu Lu, Xuedi Cao, Xiaomei Yang, Qiong Qin, Ran Song, Songlin Wang & Junqi He

  2. Beijing Laboratory of Oral Health, Capital Medical University, Beijing, People’s Republic of China

    Haibo Wang & Songlin Wang

  3. Laboratory for Clinical Medicine, Capital Medical University, Beijing, People’s Republic of China

    Haibo Wang, Xiaomei Yang, Qiong Qin, Ran Song & Junqi He

  4. Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China

    Lijie Zhang

  5. Department of Interventional Radiology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China

    Duiping Feng

  6. Salivary Gland Disease Center and Molecular Laboratory for Gene Therapy and Tooth Regeneration, School of Stomatology, Capital Medical University, Beijing, People’s Republic of China

    Songlin Wang

  7. Department of Pathology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China

    Tao Bai

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Contributions

Conceptualization: JH and HW; data curation: LZ, HL and HW; methodology: HW and LZ; investigation: RS and QQ; validation: XY, DF and SW; visualization: HW and WL; formal analysis: XC and YY; project administration: SW and JH; resources: TB; supervision: JH and TB; funding acquisition: JH and HW; writing—original draft: HL and HW; writing—review & editing: JH and TB.

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Correspondence to Tao Bai or Junqi He.

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Ethics approval and consent to participate

Animal experiments were conducted in compliance with the National Institutes of Health guidelines for the Care and Use of Laboratory Animals and approved by the Animal Use and Care Committee of Capital Medical University (approval numbers AEEI-2020-133 and AEEI-2018-201). The research involving ccRCC samples was approved by the Ethics Committee of Capital Medical University (2017SY09) and the First Hospital of Shanxi Medical University (2022HLL001).

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Wang, H., Zhang, L., Liu, H. et al. PDZK1 confers sensitivity to sunitinib in clear cell renal cell carcinoma by suppressing the PDGFR-β pathway. Br J Cancer 131, 347–360 (2024). https://doi.org/10.1038/s41416-024-02725-4

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