• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

MASTL 通过调控 EGFR 信号通路影响胰腺癌的进展。

MASTL regulates EGFR signaling to impact pancreatic cancer progression.

机构信息

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.

College of Community Health Sciences, Alabama Life Research Institute, The University of Alabama, Tuscaloosa, AL, USA.

出版信息

Oncogene. 2021 Sep;40(38):5691-5704. doi: 10.1038/s41388-021-01951-x. Epub 2021 Jul 30.

DOI:10.1038/s41388-021-01951-x
PMID:34331012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8817225/
Abstract

Pancreatic cancer (PC) remains a major cause of cancer-related deaths primarily due to its inherent potential of therapy resistance. Checkpoint inhibitors have emerged as promising anti-cancer agents when used in combination with conventional anti-cancer therapies. Recent studies have highlighted a critical role of the Greatwall kinase (microtubule-associated serine/threonine-protein kinase-like (MASTL)) in promoting oncogenic malignancy and resistance to anti-cancer therapies; however, its role in PC remains unknown. Based on a comprehensive investigation involving PC patient samples, murine models of PC progression (Kras;PdxCre-KC and Kras;p53;PdxCre-KPC), and loss and gain of function studies, we report a previously undescribed critical role of MASTL in promoting cancer malignancy and therapy resistance. Mechanistically, MASTL promotes PC by modulating the epidermal growth factor receptor protein stability and, thereupon, kinase signaling. We further demonstrate that combinatorial therapy targeting MASTL promotes the efficacy of the cell-killing effects of Gemcitabine using both genetic and pharmacological inhibitions. Taken together, this study identifies a key role of MASTL in promoting PC progression and its utility as a novel target in promoting sensitivity to the anti-PC therapies.

摘要

胰腺癌（PC）仍然是癌症相关死亡的主要原因，主要是由于其固有的治疗抵抗潜力。当与传统抗癌疗法联合使用时，检查点抑制剂已成为有前途的抗癌药物。最近的研究强调了壁激酶（微管相关丝氨酸/苏氨酸蛋白激酶样（MASTL））在促进致癌恶性肿瘤和对癌症疗法的耐药性方面的关键作用；然而，其在 PC 中的作用尚不清楚。基于涉及 PC 患者样本的全面调查、PC 进展的小鼠模型（Kras;PdxCre-KC 和 Kras;p53;PdxCre-KPC）以及功能丧失和获得研究，我们报告了 MASTL 在促进癌症恶性肿瘤和治疗耐药性方面的先前未描述的关键作用。从机制上讲，MASTL 通过调节表皮生长因子受体蛋白稳定性并由此调节激酶信号来促进 PC 的发生。我们进一步证明，针对 MASTL 的联合治疗通过遗传和药理学抑制作用促进了吉西他滨的细胞杀伤作用的疗效。总之，这项研究确定了 MASTL 在促进 PC 进展中的关键作用及其作为促进对 PC 治疗敏感性的新型靶标的效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/b098bb6892ea/nihms-1758470-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/2b9013653a3e/nihms-1758470-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/b2f2a42657f3/nihms-1758470-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/9934becb4f67/nihms-1758470-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/e311723d8b80/nihms-1758470-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/b513eee4228e/nihms-1758470-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/c55ba8fb0b78/nihms-1758470-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/9352fea183c0/nihms-1758470-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/bdee44471cea/nihms-1758470-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/b098bb6892ea/nihms-1758470-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/2b9013653a3e/nihms-1758470-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/b2f2a42657f3/nihms-1758470-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/9934becb4f67/nihms-1758470-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/e311723d8b80/nihms-1758470-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/b513eee4228e/nihms-1758470-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/c55ba8fb0b78/nihms-1758470-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/9352fea183c0/nihms-1758470-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/bdee44471cea/nihms-1758470-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8817225/b098bb6892ea/nihms-1758470-f0009.jpg

相似文献

1
MASTL regulates EGFR signaling to impact pancreatic cancer progression.MASTL 通过调控 EGFR 信号通路影响胰腺癌的进展。
Oncogene. 2021 Sep;40(38):5691-5704. doi: 10.1038/s41388-021-01951-x. Epub 2021 Jul 30.
2
MASTL induces Colon Cancer progression and Chemoresistance by promoting Wnt/β-catenin signaling.MASTL 通过促进 Wnt/β-catenin 信号通路诱导结肠癌进展和化疗耐药。
Mol Cancer. 2018 Aug 1;17(1):111. doi: 10.1186/s12943-018-0848-3.
3
MASTL: A novel therapeutic target for Cancer Malignancy.MASTL：癌症恶性肿瘤的新型治疗靶标。
Cancer Med. 2020 Sep;9(17):6322-6329. doi: 10.1002/cam4.3141. Epub 2020 Jul 21.
4
Mastl kinase, a promising therapeutic target, promotes cancer recurrence.Mastl激酶是一个很有前景的治疗靶点，它会促进癌症复发。
Oncotarget. 2014 Nov 30;5(22):11479-89. doi: 10.18632/oncotarget.2565.
5
Knockdown of Microtubule Associated Serine/threonine Kinase Like Expression Inhibits Gastric Cancer Cell Growth and Induces Apoptosis by Activation of ERK1/2 and Inactivation of NF-κB Signaling.敲低微管相关丝氨酸/苏氨酸激酶样蛋白表达通过激活ERK1/2和使NF-κB信号失活来抑制胃癌细胞生长并诱导凋亡。
Curr Med Sci. 2021 Feb;41(1):108-117. doi: 10.1007/s11596-021-2325-2. Epub 2021 Feb 13.
6
Hexosamine pathway inhibition overcomes pancreatic cancer resistance to gemcitabine through unfolded protein response and EGFR-Akt pathway modulation.己糖胺途径抑制通过未折叠蛋白反应和 EGFR-Akt 通路调节克服胰腺癌对吉西他滨的耐药性。
Oncogene. 2020 May;39(20):4103-4117. doi: 10.1038/s41388-020-1260-1. Epub 2020 Mar 31.
7
MASTL promotes cell contractility and motility through kinase-independent signaling.MASTL 通过激酶非依赖的信号通路促进细胞收缩和运动。
J Cell Biol. 2020 Jun 1;219(6). doi: 10.1083/jcb.201906204.
8
E2F8 confers cisplatin resistance to ER+ breast cancer cells via transcriptionally activating MASTL.E2F8通过转录激活MASTL赋予雌激素受体阳性（ER+）乳腺癌细胞顺铂耐药性。
Biomed Pharmacother. 2017 Aug;92:919-926. doi: 10.1016/j.biopha.2017.05.118. Epub 2017 Jun 8.
9
Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis.通过EGFR/FOXA2/SOX9轴选择性抑制干性可减少胰腺癌转移。
Oncogene. 2021 Jan;40(4):848-862. doi: 10.1038/s41388-020-01564-w. Epub 2020 Dec 7.
10
Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma.表皮生长因子受体抑制剂OSI-774（特罗凯）对人胰腺腺癌下游信号通路及细胞凋亡的影响
Mol Cancer Ther. 2002 Aug;1(10):777-83.

引用本文的文献

1
The balance between B55α and Greatwall expression levels predicts sensitivity to Greatwall inhibition in cancer cells.B55α与Greatwall表达水平之间的平衡预示着癌细胞对Greatwall抑制的敏感性。
Nat Commun. 2025 Aug 27;16(1):8016. doi: 10.1038/s41467-025-62943-z.
2
Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia.Eμ-TCL1小鼠的肠道微生物群分析揭示了肠道变化以及慢性淋巴细胞白血病特有的生态失调特征。
Cancer Res Commun. 2025 Aug 1;5(8):1344-1358. doi: 10.1158/2767-9764.CRC-25-0022.
3
Expression of MASTL (Greatwall) associates with good prognosis and response to radiotherapy in pharyngeal squamous cell carcinoma.

本文引用的文献

1
MASTL: A novel therapeutic target for Cancer Malignancy.MASTL：癌症恶性肿瘤的新型治疗靶标。
Cancer Med. 2020 Sep;9(17):6322-6329. doi: 10.1002/cam4.3141. Epub 2020 Jul 21.
2
Pancreatic cancer.胰腺癌。
Lancet. 2020 Jun 27;395(10242):2008-2020. doi: 10.1016/S0140-6736(20)30974-0.
3
Recent advances in the treatment of pancreatic cancer.胰腺癌治疗的最新进展。
MASTL（长城激酶）的表达与咽鳞状细胞癌的良好预后及放疗反应相关。
Transl Oncol. 2025 Aug;58:102417. doi: 10.1016/j.tranon.2025.102417. Epub 2025 May 20.
4
Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.乳腺上皮细胞中NOTCH1转运和信号传导的新决定因素。
Life Sci Alliance. 2024 Dec 11;8(3). doi: 10.26508/lsa.202403122. Print 2025 Mar.
5
IL-22 regulates MASTL expression in intestinal epithelial cells.IL-22 调节肠道上皮细胞中 MASTL 的表达。
Am J Physiol Gastrointest Liver Physiol. 2024 Aug 1;327(2):G123-G139. doi: 10.1152/ajpgi.00260.2023. Epub 2024 May 21.
6
Albendazole inhibits colon cancer progression and therapy resistance by targeting ubiquitin ligase RNF20.阿苯达唑通过靶向泛素连接酶 RNF20 抑制结肠癌的进展和治疗耐药性。
Br J Cancer. 2024 Apr;130(6):1046-1058. doi: 10.1038/s41416-023-02570-x. Epub 2024 Jan 26.
7
LHPP suppresses proliferation, migration, and invasion in hepatocellular carcinoma and pancreatic cancer by inhibiting EGFR signaling pathway.LHPP 通过抑制 EGFR 信号通路抑制肝癌和胰腺癌的增殖、迁移和侵袭。
Med Oncol. 2023 Jul 31;40(9):257. doi: 10.1007/s12032-023-02127-1.
8
Harnessing transcriptionally driven chromosomal instability adaptation to target therapy-refractory lethal prostate cancer.利用转录驱动的染色体不稳定性适应来靶向治疗抵抗性致命前列腺癌。
Cell Rep Med. 2023 Feb 21;4(2):100937. doi: 10.1016/j.xcrm.2023.100937. Epub 2023 Feb 13.
9
Identification and characterization of a first-generation inhibitor of claudin-1 in colon cancer progression and metastasis.鉴定和表征第一代 Claudin-1 抑制剂在结肠癌进展和转移中的作用。
Biomed Pharmacother. 2023 Mar;159:114255. doi: 10.1016/j.biopha.2023.114255. Epub 2023 Jan 23.
10
The MASTL-ENSA-PP2A/B55 axis modulates cisplatin resistance in oral squamous cell carcinoma.MASTL-ENSA-PP2A/B55轴调节口腔鳞状细胞癌中的顺铂耐药性。
Front Cell Dev Biol. 2022 Sep 28;10:904719. doi: 10.3389/fcell.2022.904719. eCollection 2022.
F1000Res. 2020 Feb 21;9. doi: 10.12688/f1000research.21981.1. eCollection 2020.
4
AKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation.AKT 通过磷酸化 MASTL 调节哺乳动物细胞有丝分裂进程，导致蛋白磷酸酶 2A 失活。
Mol Cell Biol. 2020 Apr 28;40(10). doi: 10.1128/MCB.00366-18.
5
An update on treatment options for pancreatic adenocarcinoma.胰腺腺癌治疗方案的最新进展。
Ther Adv Med Oncol. 2019 Sep 25;11:1758835919875568. doi: 10.1177/1758835919875568. eCollection 2019.
6
Correction: Upregulated claudin-1 expression promotes colitis-associated cancer by promoting β-catenin phosphorylation and activation in Notch/p-AKT-dependent manner.更正：上调的claudin-1表达通过Notch/p-AKT依赖性方式促进β-连环蛋白磷酸化和激活，从而促进结肠炎相关癌症。
Oncogene. 2019 Sep;38(38):6566. doi: 10.1038/s41388-019-0864-9.
7
Differential regulation of fibroblast growth factor receptor 1 trafficking and function by extracellular galectins.细胞外半乳糖凝集素对成纤维细胞生长因子受体 1 转运和功能的差异调节。
Cell Commun Signal. 2019 Jun 17;17(1):65. doi: 10.1186/s12964-019-0371-1.
8
Mouse-Derived Allografts: A Complementary Model to the KPC Mice on Researching Pancreatic Cancer In Vivo.小鼠来源的同种异体移植：一种在体内研究胰腺癌时对KPC小鼠起补充作用的模型。
Comput Struct Biotechnol J. 2019 Apr 6;17:498-506. doi: 10.1016/j.csbj.2019.03.016. eCollection 2019.
9
The WNT10B Network Is Associated with Survival and Metastases in Chemoresistant Triple-Negative Breast Cancer.WNT10B 网络与化疗耐药性三阴性乳腺癌的生存和转移相关。
Cancer Res. 2019 Mar 1;79(5):982-993. doi: 10.1158/0008-5472.CAN-18-1069. Epub 2018 Dec 18.
10
The Oncogenic Functions of MASTL Kinase.MASTL激酶的致癌功能。
Front Cell Dev Biol. 2018 Nov 23;6:162. doi: 10.3389/fcell.2018.00162. eCollection 2018.