Two-pore channel 2 (TPC2) is expressed in endolysosomes throughout the human body, as well as in melanosomes of melanocytes. Melanocytes produce pigment, i.e., melanin, which determines hair and skin color but also protects from UV light. Extensive exposure to UV light is one of the major risk factors for the development of melanoma, which develops from pigment-producing cells, i.e., melanocytes. In recent years, several human TPC2 single nucleotide polymorphisms have been identified to increase the likelihood of carriers presenting with blond hair and hypopigmentation. These variants were all characterized as gain-of-function versions of TPC2. Vice versa, the loss of function of TPC2 increases melanin production and reduces cancer hallmarks such as proliferation, migration, invasion, tumor growth, and metastasis formation. The activity of TPC2 is controlled in a complex manner, with several endogenous ligands as well as a number of interacting proteins being involved. We will discuss here the role of TPC2 in pigmentation and its potential to impact melanoma development and progression and highlight recent findings on Rab7a as an enhancer of TPC2 activity.
双孔通道2（TPC2）广泛表达于人体内的内溶酶体以及黑色素细胞的黑色素体中。黑色素细胞负责产生色素，即黑色素，它不仅决定头发和皮肤的颜色，还具有抵御紫外线的作用。长期暴露于紫外线是导致黑色素瘤发生的主要风险因素之一，而黑色素瘤正是由产生色素的细胞——即黑色素细胞——发展而来。近年来，已发现多种人类TPC2单核苷酸多态性会增加携带者出现金发和色素减退的可能性。这些变异均被鉴定为TPC2的功能获得型突变。反之，TPC2功能缺失则会增加黑色素的生成，并减少癌症特征，如增殖、迁移、侵袭、肿瘤生长和转移形成。TPC2的活性受到复杂调控，涉及多种内源性配体及相互作用蛋白。本文将探讨TPC2在色素沉着中的作用及其对黑色素瘤发生发展的潜在影响，并重点介绍Rab7a作为TPC2活性增强因子的最新发现。
肿瘤(癌症)患者之家