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Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance
Open accessAbstract
Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit. However, many patients with cancer fail to respond to compounds that target the PD-1 and PD-L1 interaction, and the underlying mechanism(s) is not well understood. Recent studies revealed that response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumour cells. Hence, it is important to understand the mechanistic pathways that control PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1-PD-L1 blockade in patients with cancer. Here we show that PD-L1 protein abundance is regulated by cyclin D-CDK4 and the cullin 3-SPOP E3 ligase via proteasome-mediated degradation. Inhibition of CDK4 and CDK6 (hereafter CDK4/6) in vivo increases PD-L1 protein levels by impeding cyclin D-CDK4-mediated phosphorylation of speckle-type POZ protein (SPOP) and thereby promoting SPOP degradation by the anaphase-promoting complex activator FZR1. Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumour-infiltrating lymphocytes in mouse tumours and in primary human prostate cancer specimens. Notably, combining CDK4/6 inhibitor treatment with anti-PD-1 immunotherapy enhances tumour regression and markedly improves overall survival rates in mouse tumour models. Our study uncovers a novel molecular mechanism for regulating PD-L1 protein stability by a cell cycle kinase and reveals the potential for using combination treatment with CDK4/6 inhibitors and PD-1-PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human cancers.
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“Moreover, several critical proteins including CMTM4, CMTM6, GSK3β, CSN5, CDK4, CDK6, and palmitoylated B3GNT3 have been shown to affect post-translational PD-L1 stability31–36.”
From PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells (2022) · cites this paper as [36]
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“the Cullin 3-SPOP E3-ligase complex can directly ubiquitinate PD-L1 in a cell-cycle dependent manner, leading to its degradation [15].”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [15]
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“First, as previously described [15], perturbation of the CUL3-SPOP complex interferes with the ubiquitination of PD-L1, directly enhancing its stability and protein expression level.”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [15]
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“we verified that perturbation of BHLH transcription factor MYC [12] and the ubiquitin ligase CUL3 [15] both increased PD-L1 protein levels, consistent with previous reports.”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [15]
In the citing paper
“CDK4 was shown to have kinase activity towards SPOP, a cullin 3 E3 ubiquitin ligase adaptor protein that can interact with PD-L1 (Zhang et al., 2018).”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Zhang et al., 2018
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“Treatment with palbociclib inhibits SPOP phosphorylation, promoting its degradation and blocking PD-L1 proteasome mediated degradation.”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Zhang et al., 2018
In the citing paper
“Combining palbociclib with a PD-1 blockade enhanced tumor regression and improved overall survival in mouse xenograft models of colon adenocarcinoma (Deng et al., 2017; Zhang et al., 2018).”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Zhang et al., 2018
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Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878
Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192461099 · Cited by 3,261
The Molecular Taxonomy of Primary Prostate Cancer
Abeshouse, A. A., Ahn, J., Akbani, R., Ally, A., Amin, S. B., Andry, C., Annala, M., Aprikian, A. G., Armenia, J., Arora, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.10.025 · Cited by 3,126
Zou, W., Wolchok, J. D., & Chen, L. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7118 · Cited by 2,400
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
Soucy, T. A., Smith, P. G., Milhollen, M. A., Berger, A. J., Gavin, J. M., Adhikari, S., Brownell, J. E., Burke, K. E., Cardin, D. P., Critchley, S., et al. (2009) · Nature · doi:10.1038/nature07884 · Cited by 1,990
Self-citationTaxol stabilizes microtubules in mouse fibroblast cells.
Schiff, P. B., & Horwitz, S. B. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.3.1561 · Cited by 1,971
Cell cycle proteins as promising targets in cancer therapy
Otto, T., & Siciński, P. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.138 · Cited by 1,931
Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer
Barbieri, C. E., Baca, S. C., Lawrence, M. S., Demichelis, F., Blattner, M., Theurillat, J.-P. P., White, T. A., Stojanov, P., Allen, E. M. V., Stransky, N., et al. (2012) · Nature Genetics · doi:10.1038/ng.2279 · Cited by 1,550
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Items 501–600 of 1,000
Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer
Wang, Y., Pattarayan, D., Huang, H., Zhao, Y., Li, S., Wang, Y., Zhang, M., Li, S., & Yang, D. (2024) · Nature Communications · doi:10.1038/s41467-024-47433-y · Cited by 20
STAG2 loss-of-function mutation induces PD-L1 expression in U2OS cells
Nie, Z., Gao, W., Zhang, Y., Hou, Y., Liu, J., Li, Z., Xue, W., Ye, X., & Jin, A.-M. (2019) · Annals of Translational Medicine · doi:10.21037/atm.2019.02.23 · Cited by 20
Obesity/Type 2 Diabetes-Associated Liver Tumors Are Sensitive to Cyclin D1 Deficiency
Luo, C., Liang, J., Sharabi, K., Hatting, M., Perry, E. A., Tavares, C. D. J., Goyal, L., Srivastava, A., Bilodeau, M., Zhu, A. X., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0106 · Cited by 20
Odan, N., Kikawa, Y., Matsumoto, H., Minohata, J., Suwa, H., Hashimoto, T., Okuno, T., Miyashita, M., Saito, M., Yamagami, K., et al. (2020) · Breast Cancer Basic and Clinical Research · doi:10.1177/1178223420983843 · Cited by 20
Zhao, L., Wang, J., Yang, W., Zhang, C., Zhang, W., & Chen, J. (2025) · Physical Chemistry Chemical Physics · doi:10.1039/d4cp04579c · Cited by 21
Niu, Y., Ding, C., Wang, Q., Yin, J., Li, L., Liu, W., Wang, X., & Huang, L. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03513-5 · Cited by 23
Wang, X., Wang, C., Yan, G., Kang, Y., Sun, G., Wang, S., Zou, R., Sun, H., Zeng, K., Song, H., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102685 · Cited by 19
Han, S., Wei, Z., Guo, T., Zou, J., & Li, F. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01730-8 · Cited by 19
RetractedTargeting micro-environmental pathways by PROTACs as a therapeutic strategy
Liu, J., Peng, Y., Inuzuka, H., & Wei, W. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.07.001 · Cited by 20
Self-citationNoji, R., Tohyama, K., Kugimoto, T., Kuroshima, T., Hirai, H., Tomioka, H., Michi, Y., Tasaki, A., Ohno, K., Ariizumi, Y., et al. (2022) · Cancers · doi:10.3390/cancers14143476 · Cited by 19
Seyhan, A. A., & Carini, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010041 · Cited by 22
Camus, V., Viailly, P., Drieux, F., Veresezan, E., Sesques, P., Haïoun, C., Durot, É., Patey, M., Rossi, C., Martin, L., et al. (2023) · Blood Advances · doi:10.1182/bloodadvances.2023011169 · Cited by 20
Chiba, M., Shimono, J., Suto, K., Ishio, T., Endo, T., Goto, H., Hasegawa, H., Maeda, M., Teshima, T., Yang, Y., et al. (2023) · Blood · doi:10.1182/blood.2023021423 · Cited by 19
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Gong, C., Yang, M., Long, H., Liu, X., Xu, Q., Qiao, L., Dong, H., Liu, Y., & Li, S. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.3.37 · Cited by 19
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Li, W., Guo, F., Zeng, R., Liang, H., Wang, Y., Xiong, W., Wu, H., Yang, C., & Jin, X. (2024) · Cancer Research · doi:10.1158/0008-5472.can-23-3704 · Cited by 19
Wang, H., Yeh, T., Chan, L., Hsu, C., & Cho, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207621 · Cited by 20
Self-citationOppelt, P., Ley, J. C., Worden, F. P., Palka, K. A., Maggiore, R. J., Liu, J., & Adkins, D. R. (2021) · Oral Oncology · doi:10.1016/j.oraloncology.2020.105164 · Cited by 18
Foffano, L., Cucciniello, L., Nicolò, E., Migliaccio, I., Noto, C., Reduzzi, C., Malorni, L., Cristofanilli, M., Gerratana, L., & Puglisi, F. (2024) · The Breast · doi:10.1016/j.breast.2024.103863 · Cited by 19
Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities
Awan, A. B., Osman, M. J. A., & Khan, O. M. (2025) · Cells · doi:10.3390/cells14020069 · Cited by 18
Dual membrane receptor degradation via folate receptor targeting chimera
Wang, Z., Li, Z., Hogstrom, J. M., Inuzuka, H., Jing, R., Yan, P., Hou, T., Qi, Y., Huang, D., Wang, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63882-5 · Cited by 18
Self-citationFu, M., Huang, Y., Peng, X., Li, X., Luo, N., Zhu, W., Yang, F., Chen, Z., Ma, S., Zhang, Y., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.790920 · Cited by 18
Self-citationChuan, D., Fan, R., Chen, B., Ren, Y., Mu, M., Chen, H., Zou, B., Dong, H., Tong, A., & Guo, G. F. (2023) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.3c07648 · Cited by 18
Kim, S.-B., Hwang, S., Cha, J.-Y., & Lee, H.-J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052939 · Cited by 19
Wang, L., Wu, Y., Kang, K., Zhang, X., Luo, R., Tu, Z., Zheng, Y., Guo, L., Wang, H., Tang, M., et al. (2024) · Translational Lung Cancer Research · doi:10.21037/tlcr-24-33 · Cited by 18
Self-citationModern approaches to kidney cancer immunotherapy
Кушлинский, Н. Е., Fridman, M. V., Morozov, A. A., Герштейн, Е. С., Григорьевна, К. З., & Matveev, V. B. (2018) · Cancer Urology · doi:10.17650/1726-9776-2018-14-2-54-67 · Cited by 18
Gu, W., Wang, L., Wu, Y., & Liu, J. (2018) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.13056 · Cited by 18
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Wang, Y., Hays, E., Rama, M., & Bonavida, B. (2019) · Cancer Drug Resistance · doi:10.20517/cdr.2019.98 · Cited by 20
Inter-tumor heterogeneity of PD-L1 status: is it important in clinical decision making?
Suda, K., & Mitsudomi, T. (2020) · Journal of Thoracic Disease · doi:10.21037/jtd-20-1661 · Cited by 18
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Nikhil, K., Kamra, M., Raza, A., Haymour, H. S., & Shah, K. (2020) · Cancers · doi:10.3390/cancers12113247 · Cited by 18
Luo, C., Hou, M., Huang, C., Wu, C., Ou‐Yang, F., Li, Q.-L., Wu, C.-C., & Pan, M. (2020) · PubMed Central · Cited by 18
Identification of vitamin B6 as a PD-L1 suppressor and an adjuvant for cancer immunotherapy
Yuan, J., Li, J., Shang, M., Fu, Y., & Wang, T. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.05.022 · Cited by 18
CDC27 Promotes Tumor Progression and Affects PD-L1 Expression in T-Cell Lymphoblastic Lymphoma
Song, Y., Song, W., Li, Z., Song, W., Wen, Y., Li, J., Xia, Q., & Zhang, M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00488 · Cited by 18
Targeting protein kinases benefits cancer immunotherapy
Zhang, Z., Bu, L., Luo, J., & Guo, J. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188738 · Cited by 18
Self-citationMevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA
Zhang, W., Pan, X., Xu, Y., Guo, H., Zheng, M., Chen, X., Wu, H., Luan, F., He, Q., Ding, L., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.04.002 · Cited by 17
Schulz, D., Feulner, L., Rubenich, D. S., Heimer, S., Rohrmüller, S., Reinders, Y., Falchetti, M., Wetzel, M., Braganhol, E., da Rocha, E. L., et al. (2023) · Molecular Oncology · doi:10.1002/1878-0261.13567 · Cited by 14
Xia, J., Xu, M., Hu, H., Zhang, Q., Yu, D., Cai, M., Geng, X., Zhang, H., Zhang, Y., Guo, M., et al. (2024) · MedComm · doi:10.1002/mco2.611 · Cited by 17
Rubenich, D. S., Domagalski, J. L., Gentil, G. F. S., Eichberger, J., Fiedler, M., Weber, F., Federlin, M., Poeck, H., Reichert, T. E., Ettl, T., et al. (2024) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12480 · Cited by 17
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Guo, Z., Dong, R. W., Wu, Y., Dong, S., & Alahari, S. K. (2025) · Oncogene · doi:10.1038/s41388-025-03378-0 · Cited by 18
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Chen, Y., Huang, M., Zhang, L., Feng, Z., Jiang, X., Yuan, L., Huang, R.-Y., Liu, B., Yu, H., Wang, Y., et al. (2020) · Chinese Journal of Natural Medicines · doi:10.1016/s1875-5364(20)30062-5 · Cited by 17
Mitosis in Cancer Cell Increases Immune Resistance via High Expression of HLA-G and PD-L1
Ullah, M., Aoudjeghout, W., Pimpie, C., Pocard, M. D., & Mirshahi, M. (2020) · Cancers · doi:10.3390/cancers12092661 · Cited by 18
Szeto, C. W., Kurzrock, R., Kato, S., Goloubev, A., Veerapaneni, S., Preble, A., Reddy, S. K., & Adashek, J. J. (2022) · ESMO Open · doi:10.1016/j.esmoop.2022.100396 · Cited by 16
Balko, J. M., & Sosman, J. A. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1356 · Cited by 17
Jiang, S., Lv, X., Ouyang, Z., Chi, H., Zeng, Y., Wang, Y., He, J., Chen, J., Chen, J., An, K., et al. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202407986 · Cited by 19
He, F., Zhang, Q., Chen, Y., Ge, S., Xie, Y., Sun, R., Wu, Y., & Xu, J. (2025) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2025.5564 · Cited by 18
Li, X., Gu, B., Wang, B., Feng, Z., Ma, Y., Li, H., Lucas, A. R., & Chen, H. (2020) · Oncology Reports · doi:10.3892/or.2020.7800 · Cited by 15
CDK13-Mediated Cell Cycle Disorder Promotes Tumorigenesis of High HMGA2 Expression Gastric Cancer
Wu, Z., Wang, M., Li, F., Wang, F., Jia, J., Feng, Z., Huo, X., Yang, J., Wen, J., Sa, R., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.707295 · Cited by 16
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Li, Y., Huang, Y., & Li, T. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2317-6_14 · Cited by 18
Self-citationSPOP in Cancer: Phenomena, Mechanisms and Its Role in Therapeutic Implications
Yang, X., & Zhu, Q. (2022) · Genes · doi:10.3390/genes13112051 · Cited by 16
Yu, N., Tian, W., Liu, C., Zhang, P., Zhao, Y., Nan, C., Jin, Q., Li, X., & Liu, Y. (2023) · Neurochemical Research · doi:10.1007/s11064-023-04014-7 · Cited by 16
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Ding, L., Guo, H., Zhang, J., Zheng, M., Zhang, W., Wang, L., Du, Q., Zhou, C., Xu, Y., Wu, H., et al. (2024) · Advanced Science · doi:10.1002/advs.202400340 · Cited by 16
Self-citationFan, P., Ma, J., & Jin, X. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.10.009 · Cited by 16
CDK4/RB/E2Fs axis as potential therapeutic target of endometrial cancer
Hu, J., Shen, J., & Sun, J. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.109870 · Cited by 18
Zhang, S., Xu, L., Feng, J., Tan, D., Zhu, Y., Hou, J., Li, W., Lv, K., Wang, W., Jiang, L., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.842351 · Cited by 18
Self-citationSPOP Targets Oncogenic Protein ZBTB3 for Destruction to Suppress Endometrial CancerPreprint
Jin, X., Wang, J., Li, Q., Zhuang, H., Yang, J., Lin, Z.-H., Lin, T., Lv, Z., Shen, L., Yan, C., et al. (2019) · SSRN Electronic Journal · doi:10.2139/ssrn.3491871 · Cited by 16
Shi, X., Zhao, X., He, Y., Zhang, L., Zheng, X., Qin, X., Li, K., Li, J., Wang, Y., Dai, L., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113961 · Cited by 15
Stangl, A., Wilner, C., Li, P., Maahs, L., Hwang, C., & Pilling, A. B. (2023) · The Prostate · doi:10.1002/pros.24481 · Cited by 15
Wang, X., Chen, C., Vuong, D., Rodrı́guez, S., Lam, V., Roleder, C., Wang, J. H., Kambhampati, S., Berger, A., Pennock, N. D., et al. (2023) · Leukemia · doi:10.1038/s41375-023-01889-x · Cited by 15
Wang, M., Zhang, Z., Li, Z., Zhu, Y., & Xu, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1226057 · Cited by 16
Self-citationThe emerging roles of PD-L1 subcellular localization in tumor immune evasion
Liu, D., Wen, C., Chen, L., Ye, M., Liu, H., Sun, X., Liang, L., Zhang, J., Shi, C., & Liu, J. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115984 · Cited by 15
Self-citationSPOP point mutations regulate substrate preference and affect its function
Deng, Y., Ding, W., Ma, K., Zhan, M., Sun, L., Zhou, Z., & Lu, L. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06565-1 · Cited by 15
Lv, L., Miao, Q., Zhan, S., Chen, P., Liu, W., Lv, J., Yan, W., Wang, D., Liu, H., Yin, J., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009444 · Cited by 15
Liu, C., Dong, F., Sun, J., Li, G., Du, R., Zuo, X., Zhang, K., Zhang, W., Wang, S., Li, X., et al. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-03021-2 · Cited by 15
Neural regulation of drug resistance in cancer treatment
Liu, D., Li, X., Chen, X., Sun, Y. H., Tang, A., Li, Z., Zheng, J., & Shi, M. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.10.001 · Cited by 15
Self-citationPGC‐1α inhibits polyamine metabolism in Cyclin E1‐driven ovarian cancer
Guo, T., Li, B., Gu, C., Chen, X., Han, M., Liu, X., & Xu, C. (2019) · Cancer Medicine · doi:10.1002/cam4.2637 · Cited by 15
Palicelli, A., Croci, S., Bisagni, A., Zanetti, E., de Biase, D., Melli, B., Sanguedolce, F., Ragazzi, M., Zanelli, M., Chaux, A., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212314 · Cited by 16
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Aspeslagh, S., Chabanon, R. M., Champiat, S., & Postel-Vinay, S. C. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.12.020 · Cited by 16
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Zhao, J., Li, Y., Zhu, J., Li, H., & Jin, X. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06592-2 · Cited by 14
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Ma, Z., Ding, Y.-L., Jing, J., Du, L., Zhang, X.-Y., Liu, H., & He, P. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174822 · Cited by 14
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Self-citationCancer-cell-intrinsic mechanisms shaping the immunosuppressive landscape of prostate cancer
Zhu, Y., Duong, L., Lu, X., & Lü, X. (2022) · Asian Journal of Andrology · doi:10.4103/aja202283 · Cited by 15
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Luo, J., Jin, G., Cui, S., Wang, H., & Liu, Q. (2024) · The Journal of Physiology · doi:10.1113/jp285871 · Cited by 14
Self-citationNew horizons in the mechanisms and therapeutic strategies for PD-L1 protein degradation in cancer
Li, Z., Yu, X., Yuan, Z., Li, L., & Yin, P. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189152 · Cited by 14
Wu, X., Chen, J., Chen, Y., Song, S., Fang, Y., Mao, S., Gao, J. L., Zhu, G., Qu, W., Zhao, Q., et al. (2024) · Advanced Science · doi:10.1002/advs.202408233 · Cited by 14
Wei, X., Yang, M. W., Zou, H., Shen, S., Li, Y., Chen, L., Liu, Y., Li, D., & Ding, J. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.02.020 · Cited by 14
Short- and Long-Term Effects of CDK4/6 Inhibition on Early-Stage Breast Cancer
Kietzman, W. B., Graham, G. T., Ory, V., Sharif, G. M., Kushner, M. H., Gallanis, G. T., Kallakury, B., Wellstein, A., & Riegel, A. T. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0231 · Cited by 14
Zhu, G., Li, X., Li, J., Zhou, W., Chen, Z., Fan, Y., Jiang, Y., Zhao, Y., Sun, G., & Mao, W. (2020) · Journal of Cancer · doi:10.7150/jca.47111 · Cited by 13
Lipid Metabolism and Immune Checkpoints
Liao, Q., Zhou, Y., Xia, L., & Cao, D. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-981-33-6785-2_12 · Cited by 14
Anti-cancer therapy with cyclin-dependent kinase inhibitors: impact and challenges
Reinius, M., & Smyth, E. C. (2021) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2021.3 · Cited by 14
Wu, A. T. H., Huang, H., Wen, Y.-T., Lawal, B., Mokgautsi, N., Huynh, T.-T., Hsiao, M., & Li, W. (2021) · Cells · doi:10.3390/cells10092391 · Cited by 14
Palicelli, A., Croci, S., Bisagni, A., Zanetti, E., de Biase, D., Melli, B., Sanguedolce, F., Ragazzi, M., Zanelli, M., Chaux, A., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212297 · Cited by 14
Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease
Wang, B.-R., Chen, Y., Kao, W.-H., Lai, C., Lin, H., & Hsieh, J. (2022) · Biomedicines · doi:10.3390/biomedicines10081872 · Cited by 19
Mavratzas, A., & Marmé, F. (2021) · Breast Care · doi:10.1159/000514561 · Cited by 14
Mani, M., Park, J. W., & Martin, T. F. J. (2025) · Cancers · doi:10.3390/cancers17111747 · Cited by 16
CNOT4 enhances the efficacy of anti‐PD‐1 immunotherapy in a model of non‐small cell lung cancer
Zhang, B., Han, S. H., Ma, H., & Chen, S. (2020) · FEBS Open Bio · doi:10.1002/2211-5463.12998 · Cited by 13
Bai, H., Padron, A. S., Deng, Y., Liao, Y., Murray, C. J., Ontiveros, C. O., Kari, S., Kancharla, A., Kornepati, A. V. R., Garcia, M. G., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-004871 · Cited by 13
Xie, D., Jiang, B., Wang, S., Wang, Q., & Wu, G. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1200466 · Cited by 15
Kong, P., Yang, H., Tong, Q., Dong, X., Yi, M.-A., & Yan, D. (2023) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-023-04949-y · Cited by 12
MFGE8 induces anti-PD-1 therapy resistance by promoting extracellular vesicle sorting of PD-L1
Wang, W., Chen, J., Wang, S., Sun, X., Yang, J. A., Yu, P., Hu, G., Wang, J., Zhang, J., Qiao, S., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101922 · Cited by 13
Self-citationPark, M. N., Choi, J., Fahim, M. M. H., Asevedo, E. A., Nurkolis, F., Ribeiro, R. I. M. D. A., Kang, H. N., Kang, S., Syahputra, R. A., & Kim, B. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1504618 · Cited by 14
Ferrari, P., Schiavone, M. L., Scatena, C., & Nicolini, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26073438 · Cited by 14
Snail promotes prostate cancer migration by facilitating SPOP ubiquitination and degradation
Lv, W., Huan, M., Yang, W., Gao, Y., wang, K., Xu, S., Zhang, M., Ma, J., Wang, X., Chen, Y., et al. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.05.187 · Cited by 13
Zhao, Y., Qiu, W., Liu, J., Yuan, X., Mao, W., Yin, J., Peng, B., Liu, W., Han, S. H., & He, X. (2020) · The FASEB Journal · doi:10.1096/fj.202000861rr · Cited by 12
Progression to Metastasis of Solid Cancer
Zacksenhaus, E., & Egan, S. E. (2021) · Cancers · doi:10.3390/cancers13040717 · Cited by 13
Schulz, D., Wetzel, M., Eichberger, J., Piendl, G., Brockhoff, G., Wege, A., Reichert, T., Ettl, T., & Bauer, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313087 · Cited by 13
Molecularly Guided Drug Repurposing for Cholangiocarcinoma: An Integrative Bioinformatic Approach
Venkatraman, S., Balasubramanian, B., Pongchaikul, P., Tohtong, R., & Chutipongtanate, S. (2022) · Genes · doi:10.3390/genes13020271 · Cited by 13
Development and Strategies of CDK4/6 Inhibitors
Chen, P., Xu, Y., Li, X., Yao, H., & Lin, K. (2019) · Future Medicinal Chemistry · doi:10.4155/fmc-2019-0062 · Cited by 13
Hsieh, H.-C., Ling, L.-L., & Yi-Ching, W. (2026) · Journal of Biomedical Science · doi:10.1186/s12929-025-01202-1 · Cited by 17
Opposing Roles of SPOP Mutations in Human Prostate and Endometrial Cancers
Cavalcante, L. L., Deshmukh, S. K., Ribeiro, J. R., Carneiro, B. A., Dizon, D. S., Angara, K., Mattox, T. E., Wu, S. K., Xiu, J., Walker, P., et al. (2023) · JCO Precision Oncology · doi:10.1200/po.23.00088 · Cited by 13
Cell fusion upregulates PD-L1 expression for evasion from immunosurveillance
Tajima, Y., Shibasaki, F., & Masai, H. (2023) · Cancer Gene Therapy · doi:10.1038/s41417-023-00693-0 · Cited by 12
Metadata
- Authors
- Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., Guo, J., Huang, Y.-H., Fan, C., Ren, S., Sun, Y., Freeman, G. J., Sicinski, P., & Wei, W.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Second Military Medical University (CN)
- Corresponding author
- Freeman, Gordon J.
- Wei, Wenyi
- ORCID
- Venue
- Nature
- Published
- 2017-11-16
- Volume
- 553
- Issue
- 7686
- Pages
- 91-95
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5754234
- OpenAlex
- W2769376007
- Cited by
- 1,013
- References
- 43
- Citations by year
- 2026: 81 · 2025: 123 · 2024: 138 · 2023: 140 · 2022: 134 · 2021: 157 · 2020: 118 · 2019: 78 · 2018: 43
- FWCI
- 28.82
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-07-03)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Cancer Institute (R01CA190509, R01CA229307, R01CA200573, K99CA212292, R01CA177910, P50CA101942, R01CA132740, R01CA202634, P01CA080111, R01CA200651, R01CA083688)
- National Institute of General Medical Sciences (R01GM094777, R01GM089763)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- PD-L1, anti-PD-1 therapy, CDK4/6 inhibitors, FZR1, proteasomal degradation, polyubiquitination, tumor immune evasion, immune checkpoint blockade, combination immunotherapy, tumor immune microenvironment
- MeSH terms
- Animals, Cell Cycle, Cell Line, Female, Humans, Immunologic Surveillance, Male, Neoplasms, Nuclear Proteins, Phosphorylation, Prostatic Neoplasms, Repressor Proteins, Lymphocytes, Tumor-Infiltrating, Tumor Escape, Cullin Proteins, Proteasome Endopeptidase Complex, 14-3-3 Proteins, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Mice, Protein Stability, Cyclin D, Proteolysis, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Cdh1 Proteins
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