Abstract
Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignant tumors with an increasing incidence. Studies have shown that Yes-associated protein (YAP) participates in the development of a variety of tumors as an oncogene, but to our knowledge its role in cSCC has not been reported. In this study, we used immunohistochemistry to show that YAP expression was elevated in cSCC samples of different stages versus in normal skin and that it was well correlated with the progression of the disease. Down-regulation of YAP in cSCC cell lines A431 and SCL-1 inhibited cell proliferation by inducing growth arrest during the G1/S phase transition, promoted apoptosis, and reduced invasion and migration abilities invitro. Conversely, overexpression of YAP promoted cell proliferation and protected cells against basal and chemotherapy-induced apoptosis. These oncogenic effects of YAP were associated with activation of the RAS protein and its downstream AKT and ERK. Using a mouse xenograft model, we further showed that YAP depletion inhibited cSCC tumor growth invivo. Our results suggested that YAP is involved in the carcinogenesis and development of cSCC and that it may serve as a biomarker or therapeutic target of this disease.
Highlights
Cutaneous squamous cell carcinoma is a kind of malignant tumor derived from keratinocytes of the epidermis or appendages
Yes-associated protein (YAP) protein expression is up-regulated in several Cutaneous squamous cell carcinoma (cSCC) cell lines including A431, HSC-1, and SCL-1 compared with the primary human epidermal keratinocytes (Figure 1g)
We provided evidence that YAP expression correlated with cSCC progression and that YAP promoted cSCC cell proliferation, survival, and migration via activation of RAS signaling
Summary
Cutaneous squamous cell carcinoma (cSCC) is a kind of malignant tumor derived from keratinocytes of the epidermis or appendages. It is the second most common nonmelanoma skin cancer; it accounts for 15e20% of all cutaneous. Yes-associated protein (YAP) was originally identified in Drosophila species as a key component of the Hippo pathway, which regulates tissue growth and organ size during development (Sudol, 1994; Zeng and Hong, 2008). YAP is activated and translocates to the nucleus, where it functions as a coactivator of many transcription factors such as TEAD1-4, SMADs, p73, RUNX, and TBX5 and regulates cell proliferation, apoptosis, and migration (Yu and Guan, 2013; Zhao et al, 2008).
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