HOXC10 promotes growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway

Abstract

Homeobox C10 (HOXC10) has been reported to participate in various cancers. However, the involvement of HOXC10 in melanoma is still remains unknown. Here, we attempted to determine whether HOXC10 can affect the development of melanoma. We separated melanoma tissues and the matched tumor-adjacent normal tissues from melanoma patients, and examined HOXC10 expression in the melanoma cells and tissues. Comparing with the tumor-adjacent normal tissues, HOXC10 was up-regulated in melanoma tissues. Melanoma cells also displayed an up-regulation of HOXC10. Moreover, HOXC10 overexpression promoted cell proliferation, clone formation and inhibited apoptosis of melanoma cells. HOXC10 up-regulation also enhanced migration, invasion and epithelial-mesenchymal transition (EMT) in melanoma cells. Additionally, HOXC10 accelerated Slug expression by interacting with Slug, and activating the promoter of Slug. Slug activated the YAP/TAZ signaling pathway, which was reversed by HOXC10 silencing. The in vitro assays demonstrated that inhibition of HOXC10 significantly repressed tumor growth and lung metastasis of melanoma in mice by inhibiting Slug and YAP/TAZ signaling pathway. In conclusion, this work demonstrated that HOXC10 promoted growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway. Therefore, this study suggests that inhibition of HOXC10 has therapeutic potential in melanoma.

Keratinocyte desmosomal cadherin Desmoglein 1 as a mediator and target of paracrine signaling in the melanoma niche

“…While Grhl1 has been shown to regulate epidermal homeostasis by controlling the differentiation program and barrier function (Wilanowski et al, 2008), a role in melanoma development has not been reported. Likewise, Slug has been linked to melanoma cell metastasis but not in the creation of a pro-melanoma keratinocyte compartment (Miao et al, 2021; Shirley et al, 2012). Importantly, while increased Slug likely plays additional roles in shaping the early melanoma tumor environment, genetic targeting of Dsg1 is sufficient to initiate the signaling cascade that stimulates increased melanoma cell movement in vitro .…”