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基因组分析识别了MARK3和STK10作为皮膜黑色素瘤的潜在治疗点

Usman Baqai¹, Alison M Kurimchak², Isabella V Trachtenberg¹

¹Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

The Journal of biological chemistry

|November 3, 2023

概括

研究人员确定了新的激酶,MARK3和STK10,由Gαq/11信号调节. 向这些激酶可能为转移性阴道黑色素瘤提供新的治疗策略.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
信号转导信号转导

背景情况:

卵膜黑色素瘤经常含有GNAQ/GNA11突变,激活MAPK信号传递.
目前对转移性阴膜黑色素瘤的向治疗方法有限.
"黑暗基因组"是潜在的治疗点的一个尚未探索的来源.

研究的目的:

为了识别由Gαq/11信号调节的新激酶在皮膜黑色素瘤中.
探索针对这些新发现的激酶的治疗潜力.

主要方法:

用Gαq/11抑制剂 (YM-254890) 治疗了GNAQ突变皮膜黑色素瘤细胞系.
使用多重激酶抑制剂和质谱仪进行了激酶信号蛋白质查.
使用siRNA屏幕来评估酶淘汰对细胞生长和蛋白质表达的影响.
分析了RNA测序和蛋白质组数据,以了解已识别的激酶的Gαq信号调节.

主要成果:

在抑制Gαq/11时观察到22个激酶的下调.
抑制MARK3 (微管亲和调节激酶3) 和STK10 (氨酸/氨酸激酶10) 显著降低了皮膜黑色素瘤细胞的生长.
马克3 Knockdown,但不是STK10,减少了ERK1/2酸化.
发现Gαq信号调节STK10表达和MARK3活动.

结论:

STK10和MARK3涉及Gαq/11瘤性途径在皮膜黑色素瘤.
这些激酶代表了转移性脑膜黑色素瘤的潜在新型治疗点.
对MARK3和STK10进行进一步的研究是有必要的,以便进行治疗开发.

关键词:

癌症癌症癌症癌症癌症 G 蛋白质蛋白质是一种蛋白质关氨酸核酸结合蛋白G (((q) 亚单元α.黑色素瘤是一种黑色素瘤.微管中的亲和关系调节激酶3 基激活蛋白激酶 (MAPK) 是一种激活蛋白激酶.蛋白质组学蛋白质组学氨酸/氨酸-蛋白质激酶10

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