黑色素瘤是一种侵袭性癌症，通常源自表皮基底层中的黑素细胞的转化，此处黑素细胞与周围的角质细胞直接接触。角质细胞在塑造黑色素瘤肿瘤微环境中的作用尚未得到充分研究。我们先前的研究显示，角质细胞特异性的cadherin脱屑蛋白1（Dsg1）的暂时丧失可以控制正常黑素细胞与角质细胞之间的旁分泌信号，从而刺激保护性晒黑反应。本文提供证据，表明黑色素瘤细胞利用分泌因子扰乱周围角质细胞中的Dsg1表达的细胞间通讯，进而激活依赖于CXCL1/CXCR2信号的角质细胞自身的旁分泌信号，增强黑色素瘤的扩散。证据表明，黑色素瘤细胞的旁分泌信号增加转录抑制因子Slug的水平，进而降低Dsg1转录激活因子Grhl1的表达。这些数据证明了黑色素瘤细胞与角质细胞之间的旁分泌相互作用导致角质细胞Dsg1持续减少，进而助长与肿瘤恶化相关的黑色素瘤细胞运动。2023年Burks等人发现。

Melanoma is an aggressive cancer typically arising from transformation of melanocytes residing in the basal layer of the epidermis, where they are in direct contact with surrounding keratinocytes. The role of keratinocytes in shaping the melanoma tumor microenvironment remains understudied. We previously showed that temporary loss of the keratinocyte-specific cadherin, Desmoglein 1 (Dsg1), controls paracrine signaling between normal melanocytes and keratinocytes to stimulate the protective tanning response. Here, we provide evidence that melanoma cells hijack this intercellular communication by secreting factors that keep Dsg1 expression low in the surrounding keratinocytes, which in turn generate their own paracrine signals that enhance melanoma spread through CXCL1/CXCR2 signaling. Evidence suggests a model whereby paracrine signaling from melanoma cells increases levels of the transcriptional repressor Slug, and consequently decreases expression of the Dsg1 transcriptional activator Grhl1. Together, these data support the idea that paracrine crosstalk between melanoma cells and keratinocytes resulting in chronic keratinocyte Dsg1 reduction contributes to melanoma cell movement associated with tumor progression.© 2023 Burks et al.