Zaidi M Raza, Soboloff Jonathan
Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Department of Cancer & Cellular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA.
Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Department of Cancer & Cellular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA.
Cell Calcium. 2025 Jan;125:102989. doi: 10.1016/j.ceca.2024.102989. Epub 2024 Dec 26.
Recent findings by Abrahamian et al. (2024) provides new insights into the relationship between Two Pore Channel 2 (TPC2) activity and the development and progression of melanoma. Melanocyte inducing transcription factor (MITF) is a critical regulator of both melanocyte and melanoma behavior. Abrahamian et al. (2024) show that MITF-high melanoma requires BOTH Rab7a and TPC2 for proliferation, invasion and metastasis. They further identify Wnt signaling as the mediator of this phenomenon; Rab7a induces TPC2 activity in lysosomes and melanosomes, which regulates GSK-3β stability, thereby determining whether β-catenin escapes degradation and translocates to the nucleus to transcribe the MITF gene. These observations provide new insights into the relationship between ion channel function, lysosomal/melanosomal activity and control for oncogenesis and disease progression in melanoma.
亚伯拉罕等人（2024年）最近的研究结果为双孔通道2（TPC2）活性与黑色素瘤的发生和发展之间的关系提供了新的见解。黑素细胞诱导转录因子（MITF）是黑素细胞和黑色素瘤行为的关键调节因子。亚伯拉罕等人（2024年）表明，MITF高表达的黑色素瘤在增殖、侵袭和转移方面同时需要Rab7a和TPC2。他们进一步确定Wnt信号传导是这一现象的介导因素；Rab7a在溶酶体和黑素小体中诱导TPC2活性，这调节了GSK-3β的稳定性，从而决定β-连环蛋白是否逃避降解并转运到细胞核以转录MITF基因。这些观察结果为离子通道功能、溶酶体/黑素小体活性与黑色素瘤肿瘤发生和疾病进展控制之间的关系提供了新的见解。
