MYH9 suppresses melanoma tumorigenesis, metastasis and regulates tumor microenvironment
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ORIGINAL PAPER
MYH9 suppresses melanoma tumorigenesis, metastasis and regulates tumor microenvironment Satyendra Kumar Singh1 · Sunita Sinha1,2 · Jyotirmayee Padhan1 · Nitish Jangde1 · Rashmi Ray1 · Vivek Rai1 Received: 10 June 2020 / Accepted: 22 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Non-muscle myosin IIA heavy chain (MYH9) has been implicated in many physiological and pathological functions including cell adhesion, polarity, motility to cancer. However, its role in melanoma remains unexplored. The aim of our study was to evaluate the role of MYH9 in melanoma tumor development and metastasis and further to find out the potential underlying mechanisms. In this study, we evaluated the in vitro migratory and invasive properties and in vivo tumor development and metastasis in C57BL/6 mice by silencing MYH9 in B16F10 melanoma cells. Knocking down MYH9 enhanced migration and invasiveness of B16F10 cells in vitro. Furthermore, MYH9 silencing accelerated tumor growth and metastasis in melanoma subcutaneous and intravenous mouse models. Next, oncogenes analysis revealed epithelial–mesenchymal transition and Erk signaling pathway are being regulated with MYH9 expression. Finally, MYH9 silencing in B16F10 cells modulates the tumor microenvironment by manipulating the leukocytes and macrophages infiltration in tumors. These findings established the opposing role of MYH9 as a tumor suppressor in melanoma suggesting specific MYH9 based approaches in therapeutics. Keywords MYH9 · Melanoma · Tumorigenesis · Tumor microenvironment
Introduction Melanoma is a highly aggressive cancer originates in melanocytes (pigment producing cells), primarily resides in the skin. Melanoma represents around 4% of all skin cancers; however, it contributes most to skin cancer-related mortality (approximately 80%). Melanoma can metastasize in any organ such as lung, liver, lymph nodes and gastrointestinal tract [1, 2]. Tumor metastasis/spread of cancer cells to different organs throughout the body is one pf the primary cause of cancer-related deaths (estimated ~ 90%) worldwide Satyendra Kumar Singh and Sunita Sinha contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12032-020-01413-6) contains supplementary material, which is available to authorized users. * Vivek Rai [email protected] 1
Laboratory of Vascular Immunology, Institute of Life Sciences, Bhubaneswar 751023, India
Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
2
[3]. Cancer cells metastasis is a complex and multistep process that involves the penetration of cancer cells through the basement membranes and extracellular matrix to invade adjacent tissues and metastasize via the circulatory system to extravasate, attach, proliferate and form a new tumor in distant tissue [4, 5]. Non-muscle-myosin-II (NMII) is one of the members of myosin superfamily that is represented by fifteen different classes. NMII is the conventional
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