LEM domain containing 1 promotes pancreatic cancer growth and metastasis by p53 and mTORC1 signaling pathway.
LEM domain containing 1 promotes pancreatic cancer growth and metastasis by p53 and mTORC1 signaling pathway.
复制标题
LEM结构域1通过p53和mTORC1信号通路促进胰腺癌生长和转移
DOI：
10.1080/21655979.2022.2047404
复制
发表时间：
2022-03
期刊：
影响因子：
4.9
通讯作者：
Tang, Liming
中科院分区：
文献类型：
--
作者：
Cao, Xiang;Yao, Na;Zhao, Zidan;Fu, Yue;Hu, Yuting;Zhu, Ping;Shi, Weihai;Tang, Liming
摘要胰腺癌(PC)是一种起源于胰管上皮的常见恶性肿瘤，具有致命性最强、预后最差的特点。LEM结构域包含1(LEMD1)在多种肿瘤组织中过表达，在肿瘤的发生发展中起关键作用。然而，人们对LEMD1在PC中的潜力知之甚少。在这项研究中，我们探讨了LEMD1在PC中的临床价值以及潜在的作用和机制。我们首次发现LEMD1在PC中表达上调，并且与PC患者的总体无病生存期呈负相关。在该功能中，LEMD1基因敲除抑制癌细胞的生长、迁移和侵袭，而LEMD1过表达则促进肿瘤的侵袭性。体内实验也证实了LEMD1在PC中的促瘤作用。从机制上讲，GSEA证实LEMD1通过抑制P53和激活mTORC1信号通路，促进PC的侵袭性，并影响细胞周期失调和细胞凋亡抵抗。总之，LEMD1可作为预测PC预后的有价值的候选基因和潜在的治疗靶点。缩写：ATCC：美式培养库；CCK-8：细胞计数试剂盒8；CDK：细胞周期蛋白依赖激酶；CTA：肿瘤-睾丸抗原；DMEM：Dulbecco‘s改良的Eagle’s培养液；ECL：增强化学发光；FBS：胎牛血清；GEO：基因表达总括；LEMD1：包含1的LEM结构域；mTOR：雷帕霉素的哺乳动物靶点；NC：阴性对照；PC：胰腺癌；PVDF：聚偏二氟乙烯膜；QRT-PCR：定量实时聚合酶链式反应；十二烷基硫酸钠-PAGE；SD：标准差；Skp2：S相相关蛋白；2TAA：肿瘤相关抗原；TBST：Tris-Buffed生理盐水吐温-20；TCGA：癌症基因组图谱。图形摘要
ABSTRACT Pancreatic cancer (PC) is a common type of malignancy originating from the epithelium of the pancreatic duct, with the most lethal feature and worst prognosis. LEM domain containing 1 (LEMD1) is overexpressed in multiple tumor tissues and plays a key role in cancer carcinogenesis and progression. However, little is known about the potential of LEMD1 in PC. In this study, we explored the clinical values, as well as the potential roles and mechanisms of LEMD1 in PC. We, for the first time, showed that LEMD1 was upregulated in PC and negatively correlated with the overall and disease-free survival of patients with PC. Of the function, LEMD1 knockdown inhibited cancer cell growth, migration and invasion, while LEMD1 overexpression promoted tumor aggressiveness. The tumor-promoting influences of LEMD1 in PC were also proved by in vivo assays. Mechanistically, GSEA identified that LEMD1 promoted PC aggressiveness, as well as affecting cell cycle dysregulation and apoptosis resistance, by p53 suppression and the activation of the mTORC1 signal pathway. In short, LEMD1 could serve as a valuable prognostic candidate and a potential therapeutic target of PC. Abbreviations: ATCC: American Type Culture Collection; CCK-8: Cell counting kit 8; CDK: Cyclin-dependent kinases; CTA: Cancer-testis antigen; DMEM: Dulbecco’s Modified Eagle’s Medium; ECL: enhanced chemiluminescence; FBS: Fetal bovine serum; GEO: Gene Expression Omnibus; LEMD1: LEM domain containing 1; mTOR: mammalian target of rapamycin; NC: Negative control; PC: Pancreatic cancer; PVDF: Polyvinylidene difluoride membranes; qRT-PCR: Quantitative real-time polymerase chain reaction; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis; SD: Standard deviation; SKP2: S-Phase kinase-associated protein 2; TAA: Tumor-associated antigen; TBST: Tris-buffered Saline Tween-20; TCGA: The Cancer Genome Atlas. Graphical abstract
登录
查看更多内容
GEPIA：用于癌症和正常基因表达谱和交互式分析的网络服务器。
影响因子：
14.9
作者：
Tang Z;Li C;Kang B;Gao G;Li C;Zhang Z
通讯作者：
Zhang Z
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
二甲双胍通过靶向 AMPK/mTORC1 和 mTORC2 通路诱导骨髓瘤中的自噬和 G0/G1 期细胞周期停滞
DOI：
10.1186/s13046-018-0731-5
发表时间：
2018-03-20
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Wang Y;Xu W;Yan Z;Zhao W;Mi J;Li J;Yan H
通讯作者：
Yan H
影响因子：
4
作者：
Li, Qiang;Ge, Yugang;Xu, Zekuan
通讯作者：
Xu, Zekuan
KRAS 通过 MAPK-ERK 通路抑制胰腺癌中的 RKIP，从而促进肿瘤转移和化疗耐药
影响因子：
6.4
作者：
Yang, Kege;Li, Yaqing;Chen, Yinting
通讯作者：
Chen, Yinting