Knockdown of KPNA2 inhibits autophagy in oral squamous cell carcinoma cell lines by blocking p53 nuclear translocation.
Knockdown of KPNA2 inhibits autophagy in oral squamous cell carcinoma cell lines by blocking p53 nuclear translocation.
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KPNA2 的敲低通过阻断 p53 核转位抑制口腔鳞状细胞癌细胞系的自噬
DOI：
10.3892/or.2018.6451
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发表时间：
2018-07
期刊：
影响因子：
4.2
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Lin F;Gao L;Su Z;Cao X;Zhan Y;Li Y;Zhang B
口腔鳞状细胞癌（OSCC）是美国10种最常见的肿瘤之一，占所有口腔恶性肿瘤病例的约90%。口腔鳞状细胞癌在治疗过程中难以避免化疗耐药和转移，导致患者预后差，死亡率高。自噬是一种重要的保守的细胞过程，与肿瘤细胞的耐药性和转移密切相关。本研究探讨了核转运蛋白α2（karyopherin α2，KPNA 2）在口腔鳞癌自噬过程中的作用。在CAL-27，SCC-15和Tca 8113 OSCC细胞系中，我们观察到KPNA 2的下调抑制细胞迁移和顺铂耐药性，使用伤口愈合，Transwell和CCK-8测定。此外，Western印迹分析和透射电子显微镜（TEM）分析的结果表明，敲低KPNA 2抑制自噬。我们证实了用抗自噬剂抑制自噬可以降低OSCC细胞的迁移和顺铂耐药性。我们推测，KPNA 2基因敲低对细胞迁移和顺铂耐药的抑制可能与自噬的抑制有关。为了确定潜在的机制，进一步的实验确定KPNA 2通过调节p53核输入来影响自噬水平。因此，本研究表明KPNA 2在自噬过程中的作用可能是p53依赖性的，KPNA 2通过调节p53的转位，支持自噬，从而促进口腔鳞癌细胞的耐药和转移。
Oral squamous cell carcinoma (OSCC), one of the 10 most common types of neoplasms in the US, constitutes ~90% of all cases of oral malignancies. Chemoresistance and metastasis are difficult to avoid during the course of treatment, leading to a poor prognosis and a high mortality rate for patients with OSCC. Autophagy, a critical conserved cellular process, has been reported to be highly associated with the regulation of chemoresistance and metastasis of cancer cells. The present study investigated the role of karyopherin α2 (KPNA2), a member of the importin α family, which may serve an important role in p53 nucleocytoplasmic transport in the process of OSCC autophagy. In the CAL-27, SCC-15 and Tca8113 OSCC cell lines, we observed that the downregulation of KPNA2 suppressed cell migration and cisplatin resistance, using wound-healing, Transwell and CCK-8 assays. Additionally, the results of western blot analysis and transmission electron microscopy (TEM) analysis indicated that the knockdown of KPNA2 inhibited autophagy. We confirmed that the inhibition of autophagy with anti-autophagy agents decreased the migration and cisplatin resistance of OSCC cells. We hypothesized that the suppression of cell migration and cisplatin resistance induced by KPNA2 knockdown may be associated with the inhibition of autophagy. To identify the underlying mechanism, further experiments determined that KPNA2 affects the level of autophagy via regulating the p53 nuclear import. Thus, the present study demonstrated that the function of KPNA2 in the process of autophagy may be p53-dependent, and by regulating the translocation of p53, KPNA2 can support autophagy to promote the chemoresistance and metastasis of OSCC cells.
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影响因子：
29
作者：
Kimmelman AC;White E
通讯作者：
White E
KPNA2 通过上调 c-Myc 和下调 FOXO3a 促进上皮性卵巢癌的细胞增殖和致瘤性
影响因子：
9
作者：
通讯作者：
--
影响因子：
4.3
作者：
Galluzzi, Lorenzo;Morselli, Eugenia;Kroemer, Guido
通讯作者：
Kroemer, Guido
影响因子：
13.3
作者：
Debnath, Jayanta
通讯作者：
Debnath, Jayanta
影响因子：
6.4
作者：
Gluz, Oleg;Wild, Peter;Hartmann, Arndt
通讯作者：
Hartmann, Arndt