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TAZ的抑制作用会损害黑色素瘤细胞的迁移能力。

Inhibition of TAZ impairs the migration ability of melanoma cells.

作者信息

Zhang Hao, Tu Leijing, Ma Zhouji, Lin Yue, Tan Qian

机构信息

Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, China.

Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.

出版信息

Open Life Sci. 2023 Jun 21;18(1):20220633. doi: 10.1515/biol-2022-0633. eCollection 2023.

Abstract

Malignant melanoma (MM) is characterized by rapid growth, frequent metastasis, and high mortality. Targeted therapy for MM is still a research hotspot due to the increasing understanding of the hippo pathway. The aim of this study is to investigate the role of transcriptional coactivator with PDZ-binding motif (TAZ) in MM tumorigenesis. Based on the database analysis, we found that the median mRNA expression of TAZ (5.4) was found to be similar to that of YAP (5.5) in 473 human melanoma specimens. However, in 63 MM cell lines, the median expression of TAZ (10.8) was expressed at a higher level than that of YAP (9.5), which was then validated in A375. TAZ down-regulation by siRNA decreased the migration (72%) and invasion (74%) abilities of A375. Furthermore, the down-regulation of TAZ inhibited the proliferation of A375 without affecting apoptosis. We subsequently blocked hippo signaling with verteporfin and found that verteporfin application decreased the number of migrating (63%) and invading (69%) cells, respectively. We further found that Cyr61 declined following TAZ down-regulation. Moreover, TAZ negatively correlates with melanoma patient's overall survival. Our data proved that TAZ contributed to MM metastasis, which might be a potential therapeutic target in the future.

摘要

恶性黑色素瘤(MM)的特点是生长迅速、频繁转移且死亡率高。由于对河马通路的认识不断增加,MM的靶向治疗仍然是一个研究热点。本研究的目的是探讨具有PDZ结合基序的转录共激活因子(TAZ)在MM肿瘤发生中的作用。基于数据库分析,我们发现在473例人类黑色素瘤标本中,TAZ的中位mRNA表达量(5.4)与YAP的中位mRNA表达量(5.5)相似。然而,在63种MM细胞系中,TAZ的中位表达量(10.8)高于YAP的中位表达量(9.5),这在A375细胞中得到了验证。通过小干扰RNA(siRNA)下调TAZ可降低A375细胞的迁移能力(72%)和侵袭能力(74%)。此外,TAZ的下调抑制了A375细胞的增殖,但不影响其凋亡。随后,我们用维替泊芬阻断河马信号通路,发现应用维替泊芬可分别减少迁移细胞(63%)和侵袭细胞(69%)的数量。我们进一步发现,TAZ下调后Cyr61表达下降。此外,TAZ与黑色素瘤患者的总生存期呈负相关。我们的数据证明TAZ促进了MM的转移,这可能是未来一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dff/10290279/782a461fc18a/j_biol-2022-0633-fig001.jpg

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