TWEAK/Fn14 Interaction Confers Aggressive Properties to Cutaneous Squamous Cell Carcinoma

Abstract

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-aeindependent TNFR2 signal transduction.

TWEAK Promotes the Proliferation of Squamous Cell Carcinoma Cells Through Activating cIAP1 Signals

“…Moreover, TNFR2 is expressed in some tumor cells and directly promotes proliferation of cells (22). Both Fn14 and TNFR2 are highly expressed in several SCC cell lines, and inhibition of Fn14 or TNFR2 suppresses the growth of SCC xenografts in nude mice (7). Consistently, we found in this study that TNFR2 is highly expressed in SCC-13 cells.…”

“…Previously, we demonstrated that TWEAK induces proliferation of A431 and SCC-9 cells (SCC cell lines) (7). In this study, SCC-13 cells were utilized to investigate the effect of TWEAK on cell proliferation or apoptosis.…”

“…Recently, we found that both TWEAK and Fn14 are highly expressed in human cutaneous squamous cell carcinoma (SCC), and TWEAK/Fn14 interaction promotes the proliferation, migration, and invasion of cultured SCC cell lines (7). Inhibition of Fn14 suppresses the growth of SCC xenografts in nude mice (7). The effect of TWEAK on the fate (proliferation or apoptosis) of keratinocytes is associated with the expression profile of TNF receptor (TNFR) (8).…”

Experimental atopic dermatitis is dependent on the TWEAK/Fn14 signaling pathway

“…Protein lysates were prepared from fresh tissue or cell cultures . Samples were separated on electrophoresis gels, and then transferred onto polyvinylidene difluoride membrane (Millipore, Billerica, MA, USA).…”

Meeting Report of the 4th Annual Meeting of the Chinese Society for Investigative Dermatology: Reflections on the Rise of Cutaneous Biology Research in China

“…A paracrine mechanism underlying the oxidative stress-induced cutaneous inflammation in vitiligo. Cui et al, 2019;Jian et al, 2014;Li et al, 2017;Quan et al, 2010 (continued ) J Uitto et al Ge et al, 2016;Guo et al, 2016Guo et al, ,2011Hu et al, 2019Lin et al, 2018 Autoimmune bullous diseases…”