AbstractCuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy.

摘要铜营养不良的特征是三羧酸循环的脂酰化酶聚集，随后铁硫簇蛋白丢失，这是一种独特的铜依赖性调节细胞死亡形式。由于铜稳态失调可诱导铜营养不良，因此人们对利用铜营养不良进行癌症治疗越来越感兴趣。

However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. Here, we found that cuproptosis activates the Wnt/β-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/β-catenin pathway and cancer stem cell (CSC) properties.

然而，癌细胞逃避细胞凋亡的分子驱动因素以前是不确定的。在这里，我们发现细胞凋亡激活Wnt/β-连环蛋白途径。从机制上讲，铜结合PDK1并促进其与AKT的相互作用，从而激活Wnt/β-连环蛋白途径和癌症干细胞（CSC）特性。

Notably, aberrant activation of Wnt/β-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the β-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis.

值得注意的是，Wnt/β-连环蛋白信号传导的异常激活赋予CSC对细胞凋亡的抗性。进一步的研究表明，β-连环蛋白/TCF4转录复合物直接结合ATP7B启动子，诱导其表达。ATP7B排出铜离子，减少细胞内铜并抑制细胞凋亡。

Knockdown of TCF4 or pharmacological Wnt/β-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/β-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction..

。这些发现揭示了由Wnt/β-连环蛋白途径调节的铜稳态与铜中毒敏感性之间的联系，并提出了通过选择性铜中毒诱导进行癌症治疗的精确医学策略。。

Access through your institution

通过您的机构访问

Buy or subscribe

购买或订阅

This is a preview of subscription content, access via your institution

这是订阅内容的预览，可通过您的机构访问

Access options

访问选项

Access through your institution

通过您的机构访问

Access through your institution

通过您的机构访问

Change institution

变革机构

Buy or subscribe

购买或订阅

Subscribe to this journalReceive 12 print issues and online access251,40 € per yearonly 20,95 € per issueLearn moreBuy this articlePurchase on Springer LinkInstant access to full article PDFBuy nowPrices may be subject to local taxes which are calculated during checkout

订阅本期刊每年可收到12期印刷版和在线访问251,40欧元每期仅20,95欧元了解更多购买本文在Springer Link上购买即时访问全文PDFBuy NOW价格可能需要缴纳结帐时计算的当地税费

Additional access options:

其他访问选项：

Log in

登录

Learn about institutional subscriptions

了解机构订阅

Read our FAQs

阅读我们的常见问题

Contact customer support

联系客户支持

Fig. 1: Cuproptosis activates Wnt/β-catenin signaling.Fig. 2: The SLC31A1-copper axis regulates PDK1/AKT/GSK3β/β-catenin signaling and stemness.Fig. 3: Activation of Wnt/β-catenin pathway promotes resistance to cuproptosis in cancer stem cells.Fig. 4: TCF4 protects cancer stem cells from cuproptosis by regulating ATP7B.Fig.

图1：细胞凋亡激活Wnt/β-连环蛋白信号传导。图2:SLC31A1铜轴调节PDK1/AKT/GSK3β/β-连环蛋白信号传导和干性。图3:Wnt/β-连环蛋白途径的激活促进了癌症干细胞对细胞凋亡的抵抗。图4:TCF4通过调节ATP7B保护癌症干细胞免于凋亡。图。

5: The β-catenin/TCF4 complex activates ATP7B transcription.Fig. 6: TCF4 deficiency or Wnt signaling inhibition enhances the anticancer activity of elesclomol-Cu in vivo.Fig. 7: Model for regulation of cuproptosis sensitivity by Wnt/β-catenin signaling in cancer cells..

5： β-连环蛋白/TCF4复合物激活ATP7B转录。图6:TCF4缺陷或Wnt信号传导抑制增强了elesclomol Cu在体内的抗癌活性。图7：癌细胞中Wnt/β-连环蛋白信号传导调节细胞凋亡敏感性的模型。。

Data availability

数据可用性

RNA-seq and CUT&Tag data have been deposited in GEO under the following accession numbers: GSE248083, GSE248084, and GSE248246.

RNA-seq和CUT＆Tag数据已以以下登录号保存在GEO中：GSE248083，GSE248084和GSE248246。

ReferencesGe E, Bush A, Casini A, Cobine P, Cross J, DeNicola G, et al. Connecting copper and cancer: from transition metal signalling to metalloplasia. Nat Rev Cancer. 2022;22:102–13.Article

参考文献E，Bush A，Casini A，Cobine P，Cross J，DeNicola G等。连接铜和癌症：从过渡金属信号传导到金属增生。Nat Rev癌症。2022年；22:102–13.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Brady DC, Crowe MS, Turski ML, Hobbs GA, Yao X, Chaikuad A, et al. Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature. 2014;509:492–96.Article

Brady DC，Crowe MS，Turski ML，Hobbs GA，Yao X，Chaikuad A等。铜是致癌BRAF信号传导和肿瘤发生所必需的。自然。2014年；509:492–96.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Das A, Ash D, Fouda A, Sudhahar V, Kim Y, Hou Y, et al. Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis. Nat Cell Biol. 2022;24:35–50.Article

Das A，Ash D，Fouda A，Sudhahar V，Kim Y，Hou Y等。铜转运蛋白CTR1的半胱氨酸氧化驱动VEGFR2信号传导和血管生成。Nat细胞生物学。2022年；

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Tsang T, Posimo J, Gudiel A, Cicchini M, Feldser D, Brady D. Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. Nat Cell Biol. 2020;22:412–24.Article

Tsang T，Posimo J，Gudiel A，Cicchini M，Feldser D，Brady D.铜是自噬激酶ULK1/2驱动肺腺癌的重要调节剂。Nat细胞生物学。2020年；22:412–24.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ramchandani D, Berisa M, Tavarez D, Li Z, Miele M, Bai Y, et al. Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis. Nat Commun. 2021;12:7311.Article

Ramchandani D，Berisa M，Tavarez D，Li Z，Miele M，Bai Y等。铜耗竭调节线粒体氧化磷酸化以损害三阴性乳腺癌转移。纳特公社。2021年；12： 第7311条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen L, Min J, Wang F. Copper homeostasis and cuproptosis in health and disease. Signal Transduct Target Ther. 2022;7:378.Article

Chen L，Min J，Wang F.铜稳态和铜营养不良在健康和疾病中的作用。信号传输目标Ther。2022年；7： 第378条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang W, Mo W, Hang Z, Huang Y, Yi H, Sun Z, et al. Cuproptosis: harnessing transition metal for cancer therapy. ACS Nano. 2023;17:19581–99.Article

王伟，莫伟，杭Z，黄Y，易H，孙Z，等。铜营养不良：利用过渡金属治疗癌症。ACS纳米。2023年；17： 19581-99.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Xie J, Yang Y, Gao Y, He J. Cuproptosis: mechanisms and links with cancers. Mol Cancer. 2023;22:46.Article

谢J，杨Y，高Y，何J.杯状细胞增多症：与癌症的机制和联系。摩尔癌症。2023年；22:46.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ohgami R, Campagna D, McDonald A, Fleming M. The Steap proteins are metalloreductases. Blood. 2006;108:1388–94.Article

Ohgami R，Campagna D，McDonald A，Fleming M.Steap蛋白是金属还原酶。血。2006年；108:1388–94.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Su Y, Zhang X, Li S, Xie W, Guo J. Emerging roles of the copper-CTR1 axis in tumorigenesis. Mol Cancer Res. 2022;20:1339–53.Article

Su Y，Zhang X，Li S，Xie W，Guo J.铜-CTR1轴在肿瘤发生中的新兴作用。；20： 1339-53.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

La Fontaine S, Mercer J. Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis. Arch Biochem Biophys. 2007;463:149–67.Article

La Fontaine S，Mercer J.铜ATP酶，ATP7A和ATP7B的贩运：在铜稳态中的作用。Arch Biochem Biophys。2007年；463:149–67.文章

PubMed

PubMed

Google Scholar

谷歌学者

Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022;375:1254–61.Article

Tsvetkov P，Coy S，Petrova B，Dreishpoon M，Verma A，Abdusamad M等。铜通过靶向脂酰化的TCA循环蛋白诱导细胞死亡。科学。2022年；375:1254–61.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kahlson M, Dixon S. Copper-induced cell death. Science. 2022;375:1231–32.Article

Kahlson M，Dixon S.铜诱导的细胞死亡。科学。2022年；375:1231–32.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Xiong C, Ling H, Hao Q, Zhou X. Cuproptosis: p53-regulated metabolic cell death? Cell Death Differ. 2023;30:876–84.Article

熊C，凌H，郝Q，周X.细胞凋亡：p53调节的代谢细胞死亡？细胞死亡不同。2023年；30:876–84.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Schulz V, Basu S, Freibert S-A, Webert H, Boss L, Mühlenhoff U, et al. Functional spectrum and specificity of mitochondrial ferredoxins FDX1 and FDX2. Nat Chem Biol. 2023;19:206–17.Article

Schulz V，Basu S，Freibert S-A，Webert H，Boss L，Mühlenhoff U等。线粒体铁氧还蛋白FDX1和FDX2的功能谱和特异性。Nat Chem生物。2023年；19： 206-17.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sun L, Zhang Y, Yang B, Sun S, Zhang P, Luo Z, et al. Lactylation of METTL16 promotes cuproptosis via mA-modification on FDX1 mRNA in gastric cancer. Nat Commun. 2023;14:6523.Article

Sun L，Zhang Y，Yang B，Sun S，Zhang P，Luo Z，et al。METTL16的乳酰化通过mA修饰胃癌中FDX1 mRNA促进细胞凋亡。纳特公社。2023年；14： 第6523条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cobine P, Brady D. Cuproptosis: cellular and molecular mechanisms underlying copper-induced cell death. Mol Cell. 2022;82:1786–87.Article

Cobine P，Brady D.细胞凋亡：铜诱导细胞死亡的细胞和分子机制。摩尔细胞。2022年；82:1786-87.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Jiang X, Ke J, Jia L, An X, Ma H, Li Z, et al. A novel cuproptosis-related gene signature of prognosis and immune microenvironment in head and neck squamous cell carcinoma cancer. J Cancer Res Clin Oncol. 2023;149:203–18.Article

江X，柯J，贾L，安X，马H，李Z，等。头颈部鳞状细胞癌预后和免疫微环境的新型铜营养相关基因标记。J癌症研究临床肿瘤学。2023年；149:203–18.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell. 2017;169:985–99.Article

Nusse R，Clevers H.Wnt/β-连环蛋白信号传导，疾病和新兴治疗方式。细胞。2017年；169:985–99.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Bugter J, Fenderico N, Maurice M. Mutations and mechanisms of WNT pathway tumour suppressors in cancer. Nat Rev Cancer. 2021;21:5–21.Article

Bugter J，Fenderico N，Maurice M.癌症中WNT途径肿瘤抑制因子的突变和机制。Nat Rev癌症。2021年；21:5–21.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yang L, Shi P, Zhao G, Xu J, Peng W, Zhang J, et al. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther. 2020;5:8.Article

杨丽，石鹏，赵庚，徐杰，彭伟，张杰，等。靶向癌症干细胞途径进行癌症治疗。信号传输目标Ther。2020年；5： 8、条款

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang Y, Zheng L, Shang W, Yang Z, Li T, Liu F, et al. Wnt/beta-catenin signaling confers ferroptosis resistance by targeting GPX4 in gastric cancer. Cell Death Differ. 2022;29:2190–202.Article

Wang Y，Zheng L，Shang W，Yang Z，Li T，Liu F等。Wnt/β-连环蛋白信号通过靶向胃癌中的GPX4来赋予铁浓化抗性。细胞死亡不同。2022年；29:2190–202.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12:31–46.Article

Hanahan D.癌症的标志：新的维度。癌症发现。2022年；12： 31-46.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zou Y, Zheng S, Xie X, Ye F, Hu X, Tian Z, et al. N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer. Nat Commun. 2022;13:2672.Article

邹Y，郑S，谢X，叶F，胡X，田Z等。N6-甲基腺苷调节的FGFR4减轻顽固性HER2阳性乳腺癌中的铁蛋白细胞死亡。纳特公社。2022年；13： 2672条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Huster D, Purnat TD, Burkhead JL, Ralle M, Fiehn O, Stuckert F, et al. High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease. J Biol Chem. 2007;282:8343–55.Article

Huster D，Purnat TD，Burkhead JL，Ralle M，Fiehn O，Stuckert F等。高铜选择性地改变威尔逊病小鼠模型中的脂质代谢和细胞周期机制。。2007年；282:8343–55.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Voli F, Valli E, Lerra L, Kimpton K, Saletta F, Giorgi F, et al. Intratumoral copper Modulates PD-L1 expression and influences tumor immune evasion. Cancer Res. 2020;80:4129–44.Article

Voli F，Valli E，Lerra L，Kimpton K，Saletta F，Giorgi F等。肿瘤内铜调节PD-L1表达并影响肿瘤免疫逃避。癌症研究2020；80:4129–44.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Guo J, Cheng J, Zheng N, Zhang X, Dai X, Zhang L, et al. Copper promotes tumorigenesis by activating the PDK1-AKT oncogenic pathway in a copper transporter 1 dependent manner. Adv Sci. 2021;8:e2004303.Article

郭J，程J，郑N，张X，戴X，张L等。铜通过以铜转运蛋白1依赖性方式激活PDK1-AKT致癌途径来促进肿瘤发生。高级科学。2021年；8： e2004303。条款

Google Scholar

谷歌学者

Lu J, Liu X, Li X, Li H, Shi L, Xia X, et al. Copper regulates the host innate immune response against bacterial infection via activation of ALPK1 kinase. Proc Natl Acad Sci USA. 2024;121:e2311630121.Article

Lu J，Liu X，Li X，Li H，Shi L，Xia X等。铜通过激活ALPK1激酶调节宿主对细菌感染的先天免疫反应。美国国家科学院院刊2024；121:e2311630121.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zulkifli M, Spelbring AN, Zhang Y, Soma S, Chen S, Li L, et al. FDX1-dependent and independent mechanisms of elesclomol-mediated intracellular copper delivery. Proc Natl Acad Sci USA. 2023;120:e2216722120.Article

Zulkifli M，Spelbring AN，Zhang Y，Soma S，Chen S，Li L等。电洛莫介导的细胞内铜递送的FDX1依赖性和独立机制。美国国家科学院院刊2023；120:e2216722120.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Xiao Z, Brose J, Schimo S, Ackland SM, La Fontaine S, Wedd AG. Unification of the copper(I) binding affinities of the metallo-chaperones Atx1, Atox1, and related proteins: detection probes and affinity standards. J Biol Chem. 2011;286:11047–55.Article

Xiao Z，Brose J，Schimo S，Ackland SM，La Fontaine S，Wedd AG。金属伴侣Atx1，Atox1和相关蛋白的铜（I）结合亲和力的统一：检测探针和亲和力标准。。2011年；286:11047–55.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen L, Li N, Zhang M, Sun M, Bian J, Yang B, et al. APEX2-based proximity labeling of Atox1 identifies CRIP2 as a nuclear copper-binding protein that regulates autophagy activation. Angew Chem Int Ed. 2021;60:25346–55.Article

Chen L，Li N，Zhang M，Sun M，Bian J，Yang B等。基于APEX2的Atox1邻近标记将CRIP2鉴定为调节自噬激活的核铜结合蛋白。；60:25346–55.文章

CAS

中科院

Google Scholar

谷歌学者

Wang Z, Wu VH, Allevato MM, Gilardi M, He Y, Luis Callejas-Valera J, et al. Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4. Nat Commun. 2019;10:5546.Article

Wang Z，Wu VH，Allevato MM，Gilardi M，He Y，Luis Callejas-Valera J等。烟草相关口腔癌的同系动物模型揭示了原位抗CTLA-4的活性。纳特公社。2019年；10： 第5546条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen D, Wang C. Targeting cancer stem cells in squamous cell carcinoma. Precis Clin Med. 2019;2:152–65.Article

Chen D，Wang C.靶向鳞状细胞癌中的癌症干细胞。Precis Clin Med。2019；2： 152-65.条款

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen Y, Zhao H, Liang W, Jiang E, Zhou X, Shao Z, et al. Autophagy regulates the cancer stem cell phenotype of head and neck squamous cell carcinoma through the noncanonical FOXO3/SOX2 axis. Oncogene. 2022;41:634–46.Article

Chen Y，Zhao H，Liang W，Jiang E，Zhou X，Shao Z，et al。自噬通过非典型FOXO3/SOX2轴调节头颈部鳞状细胞癌的癌症干细胞表型。致癌基因。2022年；41:634-46.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sun S, Liu S, Duan SZ, Zhang L, Zhou H, Hu Y, et al. Targeting the c-Met/FZD8 signaling axis eliminates patient-derived cancer stem-like cells in head and neck squamous carcinomas. Cancer Res. 2014;74:7546–59.Article

Sun S，Liu S，Duan SZ，Zhang L，Zhou H，Hu Y等。靶向c-Met/FZD8信号轴消除了头颈部鳞状细胞癌中患者来源的癌症干细胞样细胞。癌症研究2014；74:7546–59.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Fang L, Zhu Q, Neuenschwander M, Specker E, Wulf-Goldenberg A, Weis W, et al. A small-molecule antagonist of the β-catenin/TCF4 interaction blocks the self-renewal of cancer stem cells and suppresses tumorigenesis. Cancer Res. 2016;76:891–901.Article

Fang L，Zhu Q，Neuenschwander M，Specker E，Wulf Goldenberg A，Weis W等。β-连环蛋白/TCF4相互作用的小分子拮抗剂阻断癌症干细胞的自我更新并抑制肿瘤发生。癌症研究2016；76:891–901.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Guo B, Yang F, Zhang L, Zhao Q, Wang W, Yin L, et al. Cuproptosis induced by ROS responsive nanoparticles with elesclomol and copper combined with αPD-L1 for enhanced cancer immunotherapy. Adv Mater. 2023;35:e2212267.Article

郭B，杨F，张L，赵Q，王W，尹L，等。ROS响应纳米颗粒与elesclomol和铜联合αPD-L1诱导的细胞凋亡，用于增强癌症免疫疗法。高级材料。2023年；35:e2212267.文章

PubMed

PubMed

Google Scholar

谷歌学者

Banci L, Bertini I, Ciofi-Baffoni S, Kozyreva T, Zovo K, Palumaa P. Affinity gradients drive copper to cellular destinations. Nature. 2010;465:645–48.Article

Banci L，Bertini I，Ciofi Baffoni S，Kozyreva T，Zovo K，Palumaa P.亲和力梯度将铜驱动到细胞目的地。自然。2010年；465:645–48.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Li L, Jensen R. Understanding and overcoming immunosuppression shaped by cancer stem cells. Cancer Res. 2023;83:2096–104.Article

Li L，Jensen R.理解和克服癌症干细胞形成的免疫抑制。癌症研究2023；83:2096-104.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Castellano M, Pollock P, Walters M, Sparrow L, Down L, Gabrielli B, et al. CDKN2A/p16 is inactivated in most melanoma cell lines. Cancer Res. 1997;57:4868–75.CAS

Castellano M，Pollock P，Walters M，Sparrow L，Down L，Gabrielli B等。CDKN2A/p16在大多数黑色素瘤细胞系中均失活。；57:4868–75.CAS

PubMed

PubMed

Google Scholar

谷歌学者

Dok R, Kalev P, Van Limbergen E, Asbagh L, Vázquez I, Hauben E, et al. p16INK4a impairs homologous recombination-mediated DNA repair in human papillomavirus-positive head and neck tumors. Cancer Res. 2014;74:1739–51.Article

Dok R，Kalev P，Van Limbergen E，Asbagh L，Vázquez I，Hauben E等。p16INK4a损害人乳头瘤病毒阳性头颈部肿瘤中同源重组介导的DNA修复。癌症研究2014；74:1739-51.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Spranger S, Bao R, Gajewski T. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature. 2015;523:231–5.Article

Spranger S，Bao R，Gajewski T.黑色素瘤内在的β-连环蛋白信号传导可防止抗肿瘤免疫。自然。2015年；523:231–5.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liu Y, Sun Z. Turning cold tumors into hot tumors by improving T-cell infiltration. Theranostics. 2021;11:5365–86.Article

Liu Y，Sun Z.通过改善T细胞浸润将冷肿瘤转化为热肿瘤。。2021年；11： 5365–86.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Takeuchi Y, Tanegashima T, Sato E, Irie T, Sai A, Itahashi K, et al. Highly immunogenic cancer cells require activation of the WNT pathway for immunological escape. Sci Immunol. 2021;6:eabc6424.Article

Takeuchi Y，Tanegashima T，Sato E，Irie T，Sai A，Itahashi K等。高免疫原性癌细胞需要激活WNT途径才能进行免疫逃逸。Sci免疫。2021年；6： eabc6424.条款

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Solier S, Müller S, Cañeque T, Versini A, Mansart A, Sindikubwabo F, et al. A druggable copper-signalling pathway that drives inflammation. Nature. 2023;617:386–94.Article

Solier S，Müller S，Cañeque T，Versini A，Mansart A，Sindikubwabo F等。一种驱动炎症的可药物铜信号通路。自然。2023年；617:386–94.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Pezacki AT, Matier CD, Gu X, Kummelstedt E, Bond SE, Torrente L, et al. Oxidation state-specific fluorescent copper sensors reveal oncogene-driven redox changes that regulate labile copper(II) pools. Proc Natl Acad Sci USA. 2022;119:e2202736119.Article

Pezacki AT，Matier CD，Gu X，Kummelstedt E，Bond SE，Torrente L等。氧化态特异性荧光铜传感器揭示了癌基因驱动的氧化还原变化，可调节不稳定的铜（II）库。美国国家科学院院刊2022；119:e2202736119.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Tang D, Kroemer G, Kang R. Targeting cuproplasia and cuproptosis in cancer. Nat Rev Clin Oncol. 2024;21:370–88.Article

Tang D，Kroemer G，Kang R.针对癌症中的铜发育不良和铜营养不良。Nat Rev Clin Oncol。2024年；21:370–88.文章

PubMed

PubMed

Google Scholar

谷歌学者

Nagai M, Vo NH, Shin Ogawa L, Chimmanamada D, Inoue T, Chu J, et al. The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radic Biol Med. 2012;52:2142–50.Article

Nagai M，Vo NH，Shin Ogawa L，Chimmanamada D，Inoue T，Chu J等人。肿瘤药物elesclomol选择性地将铜转运至线粒体，以诱导癌细胞的氧化应激。Free Radic Biol Med。2012；52:2142–50.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liu Y, Li S, Wang S, Yang Q, Wu Z, Zhang M, et al. LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma. Int J Oral Sci. 2023;15:24.Article

Liu Y，Li S，Wang S，Yang Q，Wu Z，Zhang M等。LIMP-2通过促进头颈部鳞状细胞癌中自噬诱导的GSK3β降解来增强癌症干细胞样细胞特性。国际口腔科学杂志。2023年；15： 24、条款

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen L, Yang Q, Li Y, Yang L, Liu J, Li H, et al. Targeting CMTM6 suppresses stem cell-like properties and enhances antitumor immunity in head and neck squamous cell carcinoma. Cancer Immunol Res. 2020;8:179–91.Article

Chen L，Yang Q，Li Y，Yang L，Liu J，Li H，et al。靶向CMTM6抑制头颈部鳞状细胞癌的干细胞样特性并增强抗肿瘤免疫力。癌症免疫研究2020；8： 179-91.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Arnesano F, Natile G. Interference between copper transport systems and platinum drugs. Semin Cancer Biol. 2021;76:173–88.Article

Arnesano F，Natile G.铜转运系统与铂类药物之间的干扰。Semin癌症生物学。2021年；76:173-88.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Członkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, et al. Wilson disease. Nat Rev Dis Primers. 2018;4:21.Article

成员A、Litwin T、Dusek P、Ferenci P、Lutsenko S、Medici V等。Wilson病。Nat Rev Dis Primers。2018;4:21文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang S, Wu Z, Zhu S, Wan S, Zhang M, Zhang B, et al. CTLA-4 blockade induces tumor pyroptosis via CD8 T cells in head and neck squamous cell carcinoma. Mol Ther. 2023;31:2154–68.Article

Wang S，Wu Z，Zhu S，Wan S，Zhang M，Zhang B等。CTLA-4阻断剂通过头颈部鳞状细胞癌中的CD8 T细胞诱导肿瘤细胞凋亡。摩尔热。2023年；31:2154–68.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kaya-Okur H, Wu S, Codomo C, Pledger E, Bryson T, Henikoff J, et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat Commun. 2019;10:1930.Article

Kaya Okur H，Wu S，Codomo C，Slaver E，Bryson T，Henikoff J等。用于小样本和单细胞的有效表观基因组分析的切割和标记。纳特公社。2019年；10： 1930年。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Barbie D, Tamayo P, Boehm J, Kim S, Moody S, Dunn I, et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009;462:108–12.Article

Barbie D，Tamayo P，Boehm J，Kim S，Moody S，Dunn I等。系统RNA干扰显示致癌KRAS驱动的癌症需要TBK1。自然。2009年；462:108–12.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesFundingThis work was financially supported by National Natural Science Foundation of China 82273202, 82072996, 82002893, 82103670, National Key Research and Development Program 2022YFC2504200, Interdisciplinary innovative foundation of Wuhan University XNJC202303, and the Fundamental Research Funds for the Central Universities (2042022dx0003).Author informationAuthor notesThese authors contributed equally: Yuan-Tong Liu, Lei Chen.Authors and AffiliationsState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, ChinaYuan-Tong Liu, Lei Chen, Shu-Jin Li, Wu-Yin Wang, Yuan-Yuan Wang, Qi-Chao Yang, An Song, Meng-Jie Zhang, Wen-Tao Mo, Hao Li & Zhi-Jun SunDepartment of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaChuan-Yu HuAuthorsYuan-Tong LiuView author publicationsYou can also search for this author in.

下载参考文献资助这项工作得到了国家自然科学基金82273202820729968200289382103670，国家重点研究发展计划2022YFC2504200，武汉大学跨学科创新基金XNJC02303和中央大学基础研究基金（2042022dx0003）的资助。作者信息作者注意到这些作者做出了同样的贡献：刘元彤，陈磊。作者及单位武汉大学泰康生命医学中心免疫与代谢前沿科学中心口腔颌面重建与再生国家重点实验室，口腔生物医学教育部重点实验室，湖北省口腔医学重点实验室，武汉大学泰康生命医学中心，武汉，中国，刘元彤，陈磊，李淑瑾，王吴寅，王元元，齐朝阳，安松，张孟杰，莫文涛，郝丽，刘志军，武汉，华中科技大学同济医学院同济医院口腔科您也可以在中搜索此作者。

PubMed Google ScholarLei ChenView author publicationsYou can also search for this author in

PubMed Google ScholarShu-Jin LiView author publicationsYou can also search for this author in

PubMed Google ScholarShu Jin LiView作者出版物您也可以在

PubMed Google ScholarWu-Yin WangView author publicationsYou can also search for this author in

PubMed Google ScholarWu Yin WangView作者出版物您也可以在

PubMed Google ScholarYuan-Yuan WangView author publicationsYou can also search for this author in

PubMed Google ScholarYuan Yuan WangView作者出版物您也可以在

PubMed Google ScholarQi-Chao YangView author publicationsYou can also search for this author in

PubMed谷歌学者Qi Chao YangView作者出版物您也可以在

PubMed Google ScholarAn SongView author publicationsYou can also search for this author in

PubMed谷歌学者SongView作者出版物您也可以在中搜索该作者。的信息。的研究报告中找到该作者。的信息。的研究报告。的研究报告中的信息。的研究报告中的信息。的研究报告中的信息，以及在该研究报告中的信息，以及在该研究

PubMed Google ScholarMeng-Jie ZhangView author publicationsYou can also search for this author in

PubMed Google Scholarmange Jie ZhangView作者出版物您也可以在

PubMed Google ScholarWen-Tao MoView author publicationsYou can also search for this author in

PubMed Google ScholarWen Tao MoView作者出版物您也可以在

PubMed Google ScholarHao LiView author publicationsYou can also search for this author in

PubMed Google ScholarHao LiView作者出版物您也可以在

PubMed Google ScholarChuan-Yu HuView author publicationsYou can also search for this author in

PubMed Google ScholarChuan Yu HuView作者出版物您也可以在

PubMed Google ScholarZhi-Jun SunView author publicationsYou can also search for this author in

PubMed谷歌学者Zhi Jun SunView作者出版物您也可以在

PubMed Google ScholarContributionsY.T. Liu: Data curation, conceptualization, methodology, formal analysis, investigation, writing-original draft. L. Chen: Data curation, methodology, formal analysis, writing-original draft. S.J. Li: Data curation, methodology. W.Y. Wang: Investigation, methodology.

PubMed谷歌学术贡献。T、 刘：数据管理，概念化，方法论，形式分析，调查，撰写原稿。五十、 陈：数据管理，方法论，形式分析，撰写原稿。S、 J.Li：数据管理，方法论。W、 Y.Wang：调查，方法论。

Y.Y. Wang: Data curation. Q.C. Yang: Data curation. A. Song: Methodology. M.J. Zhang: Formal analysis. W.T. Mo: Formal analysis. H. Li: Supervision. C.Y. Hu: Writing-review and editing, funding acquisition. Z.J. Sun: Conceptualization, supervision, funding acquisition, writing-original draft, project administration, resources, writing-review and editing.Corresponding authorsCorrespondence to.

Y、 Y.Wang：数据管理。Q、 C.杨：数据管理。A、 宋：方法论。M、 张：形式分析。W、 T.Mo：形式分析。H、 李：监督。C、 Y.Hu：写作评论和编辑，资金获取。Z、 J.Sun：概念化，监督，资金获取，撰写原稿，项目管理，资源，写作审查和编辑。通讯作者通讯。

Chuan-Yu Hu or Zhi-Jun Sun.Ethics declarations

胡传宇或孙志军。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Ethical approval and consent to participate

道德认可和参与同意

Approval for human tissue samples utilization was granted by the Medical Ethics Committee of the School and Hospital of Stomatology, Wuhan University (2016LUNSHENZI62), following the guidelines of Declaration of Helsinki. All patients provided written informed consent. All animal experiments were carried out with the approval of the center for Animal Experiment of Wuhan University (WP20230467) and performed according to institutional guidelines..

根据赫尔辛基宣言的指导方针，武汉大学口腔医学院和医院医学伦理委员会（2016LUNSHENZI62）批准了人体组织样本的使用。所有患者均提供书面知情同意书。所有动物实验均经武汉大学动物实验中心（WP20230467）批准，并根据机构指南进行。。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplementary figuresSupplementary tablesOriginal Western Blot Data FileRights and permissionsSpringer Nature or its licensor (e.g.

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充数字补充表原始蛋白质印迹数据文件权利和许可Pringer Nature或其许可人（例如。

a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this articleCite this articleLiu, YT., Chen, L., Li, SJ.

协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Liu，YT。，Chen，L。，Li，SJ。

et al. Dysregulated Wnt/β-catenin signaling confers resistance to cuproptosis in cancer cells..

。。

Cell Death Differ (2024). https://doi.org/10.1038/s41418-024-01341-2Download citationReceived: 21 November 2023Revised: 01 July 2024Accepted: 03 July 2024Published: 10 July 2024DOI: https://doi.org/10.1038/s41418-024-01341-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

细胞死亡不同（2024）。https://doi.org/10.1038/s41418-024-01341-2Download引文接收日期：2023年11月21日修订日期：2024年7月1日接受日期：2024年7月3日发布日期：2024年7月10日OI：https://doi.org/10.1038/s41418-024-01341-2Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供