Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
J Invest Dermatol. 2019 Apr;139(4):796-806. doi: 10.1016/j.jid.2018.09.035. Epub 2018 Nov 8.
Recent studies showed that TWEAK/Fn14 signaling participates in the progression of internal malignancies. However, its role in the biological properties of cutaneous squamous cell carcinoma (SCC) remains unclear. This study was designed to explore the effect of TWEAK/Fn14 activation on cutaneous SCC as well as the relevant mechanism. The expression of TWEAK and Fn14 was determined in tissue samples of patients with cutaneous SCC. Human primary keratinocytes and SCC cell lines were cultured in vitro, receiving stimulation of TWEAK. The xenografts of SCC were generated subcutaneously in BALB/c nude mice. The results showed that both TWEAK and Fn14 were highly expressed in human cutaneous SCC. Moreover, TWEAK/Fn14 activation promoted the proliferation, migration, and invasion of cultured SCC cells. Interestingly, TNFR2 was upregulated in cultured SCC cells, and the transfection of TNFR2 small interfering RNA abrogated the effect of TWEAK on these cells. Finally, the favorable effect of TWEAK/Fn14 signals was confirmed in BALB/c nude mice with SCC xenografts. In conclusion, TWEAK/Fn14 signals contribute to the progression of cutaneous SCC, possibly involving the TNF-α-independent TNFR2 signal transduction.
最近的研究表明，TWEAK/Fn14 信号参与了内部恶性肿瘤的进展。然而，其在皮肤鳞状细胞癌（SCC）的生物学特性中的作用尚不清楚。本研究旨在探讨 TWEAK/Fn14 激活对皮肤 SCC 的影响及其相关机制。检测了皮肤 SCC 患者组织样本中 TWEAK 和 Fn14 的表达。体外培养人原代角质形成细胞和 SCC 细胞系，并接受 TWEAK 的刺激。将 SCC 的异种移植物皮下接种于 BALB/c 裸鼠。结果表明，TWEAK 和 Fn14 在人皮肤 SCC 中均高表达。此外，TWEAK/Fn14 激活促进了培养的 SCC 细胞的增殖、迁移和侵袭。有趣的是，培养的 SCC 细胞中 TNFR2 上调，TNFR2 小干扰 RNA 的转染可阻断 TWEAK 对这些细胞的作用。最后，在带有 SCC 异种移植物的 BALB/c 裸鼠中证实了 TWEAK/Fn14 信号的有利作用。总之，TWEAK/Fn14 信号有助于皮肤 SCC 的进展，可能涉及 TNF-α 非依赖性 TNFR2 信号转导。
