The skin is a highly organized tissue composed of multiple layers and cell types that require coordinated cell to cell communication to maintain tissue homeostasis. In skin cancer, this organized structure and communication is disrupted, prompting the malignant transformation of healthy cells into melanoma, basal cell carcinoma or squamous cell carcinoma tumours. One such family of channel proteins critical for cellular communication is pannexins (PANX1, PANX2, PANX3), all of which are present in the skin. These heptameric single-membrane channels act as conduits for small molecules and ions like ATP and Ca2+ but have also been shown to have channel-independent functions through their interacting partners or action in signalling pathways. Pannexins have diverse roles in the skin such as in skin development, aging, barrier function, keratinocyte differentiation, inflammation, and wound healing, which were discovered through work with pannexin knockout mice, organotypic epidermis models, primary cells, and immortalized cell lines. In the context of cutaneous cancer, PANX1 is present at high levels in melanoma tumours and functions in melanoma carcinogenesis, and both PANX1 and PANX3 expression is altered in non-melanoma skin cancer. PANX2 has thus far not been implicated in any skin cancer. This review will discuss pannexin isoforms, structure, trafficking, post-translational modifications, interactome, and channel activity. We will also outline the expression, localization, and function of pannexin channels within the diverse cell types of the epidermis, dermis, hypodermis, and adnexal structures of the skin, and how these properties are exploited or abrogated in instances of skin cancer.

中文翻译：

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游戏中的皮肤：健康和癌性皮肤中的pannexin通道

皮肤是一种高度组织化的组织，由多层和细胞类型组成，需要协调的细胞间通讯来维持组织稳态。在皮肤癌中，这种组织结构和通讯被破坏，促使健康细胞恶性转化为黑色素瘤、基底细胞癌或鳞状细胞癌。pannexins（PANX1、PANX2、PANX3）是对细胞通讯至关重要的通道蛋白家族之一，所有这些蛋白都存在于皮肤中。这些七聚体单膜通道充当小分子和离子（如 ATP 和 Ca2+）的导管，但也已被证明通过其相互作用的伙伴或信号通路中的作用而具有通道独立的功能。Pannexin 在皮肤中具有多种作用，例如在皮肤发育、衰老、屏障功能、角质形成细胞分化、炎症和伤口愈合中，这些作用是通过对 Pannexin 敲除小鼠、器官型表皮模型、原代细胞和永生化细胞系的研究发现的。在皮肤癌中，PANX1 在黑色素瘤肿瘤中高水平存在，并在黑色素瘤癌变中发挥作用，并且 PANX1 和 PANX3 表达在非黑色素瘤皮肤癌中发生改变。迄今为止，PANX2 尚未与任何皮肤癌有关。本综述将讨论泛联蛋白亚型、结构、运输、翻译后修饰、相互作用组和通道活性。我们还将概述皮肤的表皮、真皮、皮下组织和附件结构的不同细胞类型中pannexin通道的表达、定位和功能，以及这些特性在皮肤癌的情况下如何被利用或消除。