Department of Dermatology, Boston University, Boston, MA, USA.
Committee on Development, Regeneration, and Stem Cell Biology, University of Chicago, Chicago, IL, USA.
Pigment Cell Melanoma Res. 2022 Jan;35(1):52-65. doi: 10.1111/pcmr.13013. Epub 2021 Sep 1.
Yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators that have been implicated in driving metastasis and progression in many cancers, mainly through their transcriptional regulation of downstream targets. Although YAP and TAZ have shown redundancy in many contexts, it is still unknown whether or not this is true in melanoma. Here, we show that while both YAP and TAZ are expressed in a panel of melanoma cell lines, depletion of YAP results in decreased cell numbers, focal adhesions, and the ability to invade matrigel. Using non-biased RNA-sequencing analysis, we find that melanoma cells depleted of YAP, TAZ, or YAP/TAZ exhibit drastically different transcriptomes. We further uncover the ARP2/3 subunit ARPC5 as a specific target of YAP but not TAZ and that ARPC5 is essential for YAP-dependent maintenance of melanoma cell focal adhesion numbers. Our findings suggest that in melanoma, YAP drives melanoma progression, survival, and invasion.
Yes 相关蛋白 1(YAP)和 PDZ 结合基序的转录共激活因子(TAZ)是转录共激活因子,它们已被牵连到许多癌症的转移和进展中,主要是通过其对下游靶标的转录调控。尽管 YAP 和 TAZ 在许多情况下表现出冗余性,但在黑色素瘤中是否如此仍不清楚。在这里,我们表明,虽然 YAP 和 TAZ 在一系列黑色素瘤细胞系中均有表达,但 YAP 的耗竭导致细胞数量减少、焦点粘连和侵袭 Matrigel 的能力下降。通过无偏见的 RNA 测序分析,我们发现 YAP、TAZ 或 YAP/TAZ 耗竭的黑色素瘤细胞表现出截然不同的转录组。我们进一步揭示了 ARP2/3 亚基 ARPC5 是 YAP 的特异性靶标,但不是 TAZ 的靶标,并且 ARPC5 是 YAP 依赖的维持黑色素瘤细胞焦点粘连数量所必需的。我们的研究结果表明,在黑色素瘤中,YAP 驱动黑色素瘤的进展、存活和侵袭。