HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective therapies. We demonstrated that the transcription factor, HOXC6, was overexpressed in most PDACs, and its inhibition blocked PDAC tumor growth and metastasis. HOXC6 transcriptionally activated the tumor-promoting kinase MSK1. To identify the phosphorylation targets of MSK1 and the mediators of its function in AsPC1 cells, we utilized an unbiased TMT10-based phosphoproteomics analysis. To do so, we treated AsPC1 cells with MSK1 inhibitor SB-747651A and performed TMT10-based quantitative phosphoproteomics analysis and identified MSK1 phosphorylation targets.

胰腺导管腺癌（Pancreatic ductal adenocarcinoma, PDAC）是致死率最高的癌症之一，目前缺乏有效的治疗手段。本研究证实，转录因子（transcription factor）HOXC6在多数PDAC组织中呈过表达状态，抑制其表达可阻断PDAC的肿瘤生长与转移。HOXC6可转录激活促肿瘤激酶MSK1。为鉴定MSK1的磷酸化靶点及其在AsPC1细胞中发挥功能的介导因子，本研究采用基于TMT10的无偏磷酸化蛋白质组学分析方法：将AsPC1细胞用MSK1抑制剂SB-747651A处理后，开展基于TMT10的定量磷酸化蛋白质组学分析，最终鉴定得到MSK1的磷酸化靶点。