LATS1 Is a Mediator of Melanogenesis in Response to Oxidative Stress and Regulator of Melanoma Growth.

Urszula Kazimierczak,Ewelina Dondajewska,Tomasz Kolenda,Andrzej Mackiewicz,Andrzej Mackiewicz,Marianna Karwacka,Maria Zajaczkowska

doi:10.3390/ijms22063108

Urszula Kazimierczak, Ewelina Dondajewska + Show 5 more

Open Access

https://doi.org/10.3390/ijms22063108

Copy DOI

Abstract

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.

Highlights

We observed a significant decrease in all tested melanogenesis markers, including tyrosinase and microphthalmia-associated transcription factor (MITF), both on a transcript (Figure 1C), and protein (Figure 1D) levels
We discovered a new function of the central kinase of Hippo signalingLATS1
We demonstrated that LATS1 is highly involved in melanin biosynthesis as well as in tumor growth control

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Hippo signaling is an evolutionarily conserved regulator of organ size and tumorigenesis. Activation of the pathway induces the interaction of a serine/threonine kinases cascade and adaptors, resulting in the phosphorylation of the effector molecules. In humans, these proteins include the serine/threonine kinases MST1/2 and LATS1/2, and the adaptor proteins MOB1 and SAV1. LATS1/2 kinases phosphorylate transcriptional co-activator paralogs YAP1 and TAZ to regulate transcription of proliferative and apoptotic factors

Objectives

Methods

Results

Conclusion