A powerful means to understand the cellular function of corrupt oncogenic signaling programs requires perturbing the system and monitoring the downstream consequences. Here, using a unique pair of non-small cell lung cancer (NSCLC)/normal lung epithelial patient-derived cell lines (HCC4017/HBEC30KT), we systematically interrogated the remodeling of the NSCLC proteome upon treatment with 35 chemical perturbagens targeting a diverse array of mechanistic classes. HCC4017 and HBEC30KT cells differ significantly in their proteomic response to the same compound treatment. Using protein covariance analyses, we identified a large number of functional protein networks. For example, we found that a poorly studied protein, C5orf22, is a novel component of the WBP11/PQBP1 splicing complex. Depletion of C5orf22 leads to the aberrant splicing and expression of genes involved in cell growth and immunomodulation. In summary, we show that by systematically measuring the tumor adaptive responses at the proteomic level, an understanding could be generated that provides critical circuit-level biological insights for these pharmacologic perturbagens.

中文翻译：

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蛋白质组连接图，用于表征对小分子化学微扰的肿瘤适应性反应。

理解致癌的信号传导程序的细胞功能的有效手段，需要扰动系统并监测下游后果。在这里，我们使用一对独特的非小细胞肺癌（NSCLC）/正常肺上皮患者来源的细胞系（HCC4017 / HBEC30KT），在针对35种化学干扰素治疗后，系统地询问了NSCLC蛋白质组的重构机械课程。HCC4017和HBEC30KT细胞对相同化合物处理的蛋白质组反应差异显着。使用蛋白质协方差分析，我们确定了许多功能性蛋白质网络。例如，我们发现，一个研究不足的蛋白质C5orf22是WBP11 / PQBP1剪接复合体的新组成部分。C5orf22的耗尽导致参与细胞生长和免疫调节的基因的异常剪接和表达。总而言之，我们显示出通过系统地测量蛋白质组学水平上的肿瘤适应性反应，可以产生一种理解，从而为这些药理学上的不稳定因素提供关键的回路水平的生物学见解。