Caveolin-1 promotes cancer progression via inhibiting ferroptosis in head and neck squamous cell carcinoma.
Caveolin-1 promotes cancer progression via inhibiting ferroptosis in head and neck squamous cell carcinoma.
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Caveolin™1 通过抑制头颈鳞状细胞癌的铁死亡促进癌症进展
DOI：
10.1111/jop.13267
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Lu T;Zhang Z;Pan X;Zhang J;Wang X;Wang M;Li H;Yan M;Chen W
摘要背景头颈部鳞状细胞癌是一种侵袭性疾病。近年来，对HNSCC发病机制的研究和治疗方法的改进取得了很大进展，但关于铁凋亡在HNSCC进展中的作用的研究较少。本研究旨在揭示窖蛋白-1（CAV 1）-活性氧-铁凋亡轴影响HNSCC过程的潜在机制，并发现新的治疗靶点或策略。方法应用FerDb分析CAV 1在铁凋亡中的作用，并应用HNSCC的TCGA数据集分析CAV 1的临床意义。采用免疫组化、western blot和真实的实时荧光定量PCR检测HNSCC组织中caveolin-1（CAV 1）的表达。设计了三种siRNA序列以沉默HNSCC细胞中的CAV 1 mRNA。使用细胞增殖、集落形成、伤口愈合和transwell测定来检查癌细胞的增殖、迁移和侵袭。进行ROS评价和细胞内Fe 2+含量测定以检查铁凋亡水平。结果CAV 1在HNSCC中的表达高于正常组织，是铁凋亡途径的重要抑制因子之一。我们的研究表明，CAV 1在HNSCC组织中过表达，高水平的CAV 1预示着较差的预后。进一步的实验表明，CAV 1能够抑制癌细胞的铁凋亡，促进癌细胞的增殖、迁移和侵袭。结论CAV 1在HNSCC中的过表达抑制了铁凋亡的发生，导致HNSCC细胞表型的侵袭性，预后不良。CAV 1的调控途径和铁凋亡是设计HNSCC患者诊断和联合治疗策略的潜在靶点。
Abstract Background Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease worldwide. Much progress has been made in exploring mechanisms and improving the therapy of HNSCC, but only a few studies have focused on the role of ferroptosis on HNSCC progression. The current study aimed to reveal the underlining mechanisms that caveolin‐1 (CAV1)‐ROS (reactive oxygen species)‐ferroptosis axis affect the process of HNSCC and discover novo therapeutic targets or strategies. Methods The role of CAV1 in ferroptosis was analyzed by FerrDb, and its clinical significance was examined by TCGA dataset of HNSCC. The expressions of caveolin‐1 (CAV1) in HNSCC tissues were measured by immunohistochemistry, western blot, and real‐time PCR assay. Three siRNA sequences were designed to silence CAV1 mRNA in HNSCC cells. Cell proliferation, colony formation, wound‐healing, and transwell assays were used to examine the proliferation, migration, and invasion of cancer cells. ROS evaluation and intracellular Fe2+ content assays were performed to examine the levels of ferroptosis. Results Through the analysis with published data, CAV1 was found to overexpress in HNSCC than normal tissues, and was one of the vital suppressors of ferroptosis pathway. Our study showed that CAV1 was over expressed in HNSCC tissues and the high level of CAV1 predicted poorer prognosis. Further experiments indicated that CAV1 could inhibit the ferroptosis of cancer cells and promote the proliferation, migration and invasion. Conclusions Overexpression of CAV1 in HNSCC inhibited the process of ferroptosis, leading to aggressive phenotypes, as well as worse prognosis. The regulatory pathway of CAV1 and ferroptosis are potential targets for designing diagnostic and combined therapeutic strategies for HNSCC patients.
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影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
11.4
作者：
Roh, Jong-Lyel;Kim, Eun Hye;Jang, Hyejin;Shin, Daiha
通讯作者：
Shin, Daiha
DOI：
10.1158/1541-7786.mcr-11-0451
发表时间：
2012-02
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Yang G;Goltsov AA;Ren C;Kurosaka S;Edamura K;Logothetis R;DeMayo FJ;Troncoso P;Blando J;DiGiovanni J;Thompson TC
通讯作者：
Thompson TC
影响因子：
4.7
作者：
Reddel, RR
通讯作者：
Reddel, RR
影响因子：
64.8
作者：
Jiang, Le;Kon, Ning;Li, Tongyuan;Wang, Shang-Jui;Su, Tao;Hibshoosh, Hanina;Baer, Richard;Gu, Wei
通讯作者：
Gu, Wei