黑色素瘤
癌症研究
转移
肿瘤微环境
肿瘤进展
蛋白激酶B
癌变
PI3K/AKT/mTOR通路
血管生成
上皮-间质转换
基因沉默
基因敲除
癌症
生物
信号转导
细胞生长
细胞培养
细胞生物学
肿瘤细胞
基因
生物化学
遗传学
作者
S. Sunita,Satyendra Kumar Singh,Nitish Jangde,Rashmi Ray,Vivek Rai
标识
DOI:10.1038/s41419-021-04311-5
摘要
Melanoma originates from melanin-producing cells called melanocytes. Melanoma poses a great risk because of its rapid ability to spread and invade new organs. Cellular metastasis involves alteration in the gene expression profile and their transformation from epithelial to mesenchymal state. Despite of several advances, metastatic melanoma being a key cause of therapy failure and mortality remains poorly understood. p32 has been found to be involved in various physiological and pathophysiological conditions. However, the role of p32 in melanoma progression and metastasis remains underexplored. Here, we identify the role of p32 in the malignancy of both murine and human melanoma. p32 knockdown leads to reduced cell proliferation, migration, and invasion in murine and human melanoma cells. Furthermore, p32 promotes in vitro tumorigenesis, inducing oncogenes and EMT markers. Mechanistically, we show p32 regulates tumorigenic and metastatic properties through the Akt/PKB signaling pathway in both murine and human melanoma. Furthermore, p32 silencing attenuates melanoma tumor progression and lung metastasis in vivo, modulating the tumor microenvironment by inhibiting the angiogenesis, infiltration of macrophages, and leukocytes in mice. Taken together, our findings identify that p32 drives melanoma progression, metastasis, and regulates the tumor microenvironment. p32 can be a target of a novel therapeutic approach in the regulation of melanoma progression and metastasis.
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