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Lyn激酶通过PI3K/Akt信号通路抑制细胞凋亡和自噬,从而促进恶性黑色素瘤细胞的增殖。

Lyn Kinase Promotes the Proliferation of Malignant Melanoma Cells through Inhibition of Apoptosis and Autophagy via the PI3K/Akt Signaling Pathway.

作者信息

Zhang Qianqian, Meng Xianguang, Qin Guojing, Xue Xiaotong, Dang Ningning

机构信息

Department of Dermatology, Jinan Central Hospital affiliated to Shandong University, Jinan, Shandong Province, China.

Taishan Medical University, Taian, Shandong Province, China.

出版信息

J Cancer. 2019 Jan 29;10(5):1197-1208. doi: 10.7150/jca.28908. eCollection 2019.

Abstract

Melanoma is a malignant tumor of cutaneous melanocytes that is characterized by high grade malignancy, rapid progression and high mortality. Thus far, its specific etiological mechanism has been unclear. In this study, we discovered that Lyn kinase expression was up-regulated in melanoma tissues and cells. The function of Lyn was determined by knocking down its expression with a lentivirus containing Lyn shRNA and upregulating its expression with pcDNA3.1-Lyn in the melanoma cell lines M14 and A375. The results showed that Lyn knockdown could significantly inhibit the proliferation, migration and invasiveness through its inhibition of apoptosis and autophagy via the PI3K/Akt pathway in melanoma cell lines. This was further confirmed by treatment with PI3K inhibitor BEZ235. Up-regulation of Lyn promoted the expression of p-Akt and Cyclin D1. Additionally, we investigated the effects of Lyn inhibitor Bafetinib on melanoma cells and the results were consistent with Lyn knockdown. Collectively, our results indicated that Lyn plays a carcinogenic role in multiple cellular functions during melanoma development through regulating apoptosis and autophagy via the PI3K/Akt pathway and may be a valuable potential target for the clinical treatment of melanoma.

摘要

黑色素瘤是一种皮肤黑素细胞的恶性肿瘤,其特征为高度恶性、进展迅速且死亡率高。迄今为止,其具体的病因机制尚不清楚。在本研究中,我们发现Lyn激酶在黑色素瘤组织和细胞中表达上调。通过在黑色素瘤细胞系M14和A375中用携带Lyn shRNA的慢病毒敲低其表达以及用pcDNA3.1-Lyn上调其表达来确定Lyn的功能。结果表明,敲低Lyn可通过PI3K/Akt途径抑制黑色素瘤细胞系中的凋亡和自噬,从而显著抑制其增殖、迁移和侵袭能力。用PI3K抑制剂BEZ235处理进一步证实了这一点。Lyn的上调促进了p-Akt和细胞周期蛋白D1的表达。此外,我们研究了Lyn抑制剂巴非替尼对黑色素瘤细胞的影响,结果与敲低Lyn一致。总体而言,我们的结果表明,Lyn在黑色素瘤发展过程中通过PI3K/Akt途径调节凋亡和自噬,在多种细胞功能中发挥致癌作用,可能是黑色素瘤临床治疗的一个有价值的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f8c/6400685/1c0873aa10e8/jcav10p1197g001.jpg

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