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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.

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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