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在乳腺癌细胞中,分选连接蛋白14(SNX14)通过PI3K/AKT/mTOR信号级联反应抑制自噬。

SNX14 inhibits autophagy via the PI3K/AKT/mTOR signaling cascade in breast cancer cells.

作者信息

Lv Sha, Jiang Hongyan, Yu Lingyan, Zhang Yafei, Sun Liangliang, Xu Junjun

机构信息

Department of Pharmacy, Zhejiang Hospital, Hangzhou, 310013, China.

Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.

出版信息

J Mol Histol. 2024 Aug;55(4):391-401. doi: 10.1007/s10735-024-10209-1. Epub 2024 Jun 13.

DOI:10.1007/s10735-024-10209-1
PMID:38869753
Abstract

BACKGROUND

Sorting nexin 14 (SNX14) is a member of the sorting junction protein family. Its specific roles in cancer development remain unclear. Therefore, in this study, we aimed to determine the effects and underlying mechanisms of SNX14 on autophagy of breast cancer cells to aid in the therapeutic treatment of breast cancer.

METHODS

In this study, we performed in vitro experiments to determine the effect of SNX14 on breast cancer cell growth. Moreover, we used an MCF7 breast cancer tumor-bearing mouse model to confirm the effect of SNX14 on tumor cell growth in vivo. We also performed western blotting and quantitative polymerase chain reaction to identify the mechanism by which SNX14 affects breast cancer MCF7 cells.

RESULTS

We found that SNX14 regulated the onset and progression of breast cancer by promoting the proliferation and inhibiting the autophagy of MCF7 breast cancer cells. In vivo experiments further confirmed that SNX14 knockdown inhibited the tumorigenicity and inhibited the growth of tumor cells in tumor tissues of nude mice. In addition, western blotting analysis revealed that SNX14 modulate the autophagy of MCF7 breast cancer cells via the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signaling pathway.

CONCLUSION

Our findings indicate that SNX14 is an essential tumor-promoting factor in the development of breast cancer.

摘要

背景

分选连接蛋白14(SNX14)是分选连接蛋白家族的成员。其在癌症发展中的具体作用尚不清楚。因此,在本研究中,我们旨在确定SNX14对乳腺癌细胞自噬的影响及潜在机制,以辅助乳腺癌的治疗。

方法

在本研究中,我们进行了体外实验以确定SNX14对乳腺癌细胞生长的影响。此外,我们使用MCF7荷乳腺癌小鼠模型来证实SNX14在体内对肿瘤细胞生长的影响。我们还进行了蛋白质印迹法和定量聚合酶链反应,以确定SNX14影响乳腺癌MCF7细胞的机制。

结果

我们发现SNX14通过促进MCF7乳腺癌细胞的增殖和抑制其自噬来调节乳腺癌的发生和发展。体内实验进一步证实,敲低SNX14可抑制裸鼠肿瘤组织的致瘤性并抑制肿瘤细胞生长。此外,蛋白质印迹分析表明,SNX14通过磷酸肌醇3-激酶/蛋白激酶B/雷帕霉素激酶信号通路调节MCF7乳腺癌细胞的自噬。

结论

我们的研究结果表明,SNX14是乳腺癌发展过程中一种重要的肿瘤促进因子。

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本文引用的文献

1
Tumor-derived CTF1 (cardiotrophin 1) is a critical mediator of stroma-assisted and autophagy-dependent breast cancer cell migration, invasion and metastasis.肿瘤来源的 CTF1(心营养素 1)是基质辅助和自噬依赖性乳腺癌细胞迁移、侵袭和转移的关键介质。
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Engineering hyaluronic acid-based cryogels for CD44-mediated breast tumor reconstruction.用于CD44介导的乳腺肿瘤重建的工程化透明质酸基冷冻凝胶
Mater Today Bio. 2022 Jan 24;13:100207. doi: 10.1016/j.mtbio.2022.100207. eCollection 2022 Jan.
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Autosomal recessive spinocerebellar ataxia-20 due to a novel SNX14 variant in an Indian girl.
一名印度女孩因新型SNX14变异导致的常染色体隐性遗传性脊髓小脑共济失调20型
Am J Med Genet A. 2022 Jun;188(6):1909-1914. doi: 10.1002/ajmg.a.62701. Epub 2022 Feb 23.
4
SNX3 suppresses the migration and invasion of colorectal cancer cells by reversing epithelial-to-mesenchymal transition via the β-catenin pathway.分选连接蛋白3通过β-连环蛋白途径逆转上皮-间质转化,从而抑制结肠癌细胞的迁移和侵袭。
Oncol Lett. 2019 Nov;18(5):5332-5340. doi: 10.3892/ol.2019.10860. Epub 2019 Sep 12.
5
Deletion of sorting nexin 27 suppresses proliferation in highly aggressive breast cancer MDA-MB-231 cells in vitro and in vivo.缺失分选连接蛋白 27 可抑制体外和体内高侵袭性乳腺癌 MDA-MB-231 细胞的增殖。
BMC Cancer. 2019 Jun 10;19(1):555. doi: 10.1186/s12885-019-5769-z.
6
Cerebellar ataxia disease-associated Snx14 promotes lipid droplet growth at ER-droplet contacts.小脑共济失调相关蛋白 Snx14 促进内质网液滴接触点处脂滴生长。
J Cell Biol. 2019 Apr 1;218(4):1335-1351. doi: 10.1083/jcb.201808133. Epub 2019 Feb 14.
7
SNX14 mutations affect endoplasmic reticulum-associated neutral lipid metabolism in autosomal recessive spinocerebellar ataxia 20.SNX14 突变影响常染色体隐性小脑共济失调 20 型内质网相关中性脂质代谢。
Hum Mol Genet. 2018 Jun 1;27(11):1927-1940. doi: 10.1093/hmg/ddy101.
8
DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation.DDX19A可感知病毒RNA并介导NLRP3依赖性炎性小体激活。
J Immunol. 2015 Dec 15;195(12):5732-49. doi: 10.4049/jimmunol.1501606. Epub 2015 Nov 4.
9
Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction.SNX14基因的双等位基因突变会导致一种伴有综合征的小脑萎缩和溶酶体-自噬体功能障碍。
Nat Genet. 2015 May;47(5):528-34. doi: 10.1038/ng.3256. Epub 2015 Apr 6.
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SNX14 is a bifunctional negative regulator for neuronal 5-HT6 receptor signaling.分选连接蛋白14(SNX14)是神经元5-羟色胺6型受体信号传导的双功能负调节因子。
J Cell Sci. 2015 May 1;128(9):1848-61. doi: 10.1242/jcs.169581. Epub 2015 Mar 20.