Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Rokietnicka Street 8, 61-806 Poznan, Poland.
Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, Garbary Street 15, 61-866 Poznan, Poland.
Int J Mol Sci. 2021 Mar 18;22(6):3108. doi: 10.3390/ijms22063108.
The LATS1 kinase has been described as a tumor suppressor in various cancers. However, its role in melanoma has not been fully elucidated. There are several processes involved in tumorigenesis, including melanin production. Melanin content positively correlates with the level of reactive oxygen species (ROS) inside the cell. Accordingly, the purpose of the study was to assess the role of LATS1 in melanogenesis and oxidative stress and its influence on tumor growth. We have knocked down LATS1 in primary melanocytes and melanoma cells and found that its expression is crucial for melanin synthesis, ROS production, and oxidative stress response. We showed that LATS1 ablation significantly decreased the melanogenesis markers' expression and melanin synthesis in melanocyte and melanoma cell lines. Moreover, silencing LATS1 resulted in enhanced oxidative stress. Reduced melanin content in LATS1 knocked down tumors was associated with increased tumor growth, pointing to melanin's protective role in this process. The study demonstrated that LATS1 is highly engaged in melanogenesis and oxidative stress control and affects melanoma growth. Our results may find the implications in the diagnosis and treatment of pigmentation disorders, including melanoma.
LATS1 激酶在各种癌症中被描述为肿瘤抑制因子。然而，其在黑色素瘤中的作用尚未完全阐明。肿瘤发生涉及多个过程，包括黑色素生成。黑色素含量与细胞内活性氧 (ROS) 的水平呈正相关。因此，本研究旨在评估 LATS1 在黑色素生成和氧化应激中的作用及其对肿瘤生长的影响。我们已经在原代黑素细胞和黑色素瘤细胞中敲低了 LATS1，发现其表达对黑色素合成、ROS 产生和氧化应激反应至关重要。我们表明，LATS1 缺失显著降低了黑素细胞和黑色素瘤细胞系中黑色素生成标志物的表达和黑色素合成。此外，沉默 LATS1 导致氧化应激增强。LATS1 敲低肿瘤中的黑色素含量减少与肿瘤生长增加有关，表明黑色素在这个过程中具有保护作用。该研究表明，LATS1 高度参与黑色素生成和氧化应激的控制，并影响黑色素瘤的生长。我们的结果可能对包括黑色素瘤在内的色素沉着障碍的诊断和治疗具有重要意义。
