From the Department of Cancer Cell Biology, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
From the Department of Cancer Cell Biology, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Adv Biol Regul. 2020 Jan;75:100656. doi: 10.1016/j.jbior.2019.100656. Epub 2019 Sep 25.
Protein Kinase Cι (PKCι) is a major oncogene involved in the initiation, maintenance and progression of numerous forms of human cancer. In the lung, PKCι is necessary for the maintenance of the transformed phenotype of the two major forms of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC). In addition, PKCι is necessary for both LADC and LSCC tumorigenesis by establishing and maintaining a highly aggressive stem-like, tumor-initiating cell phenotype. Interestingly however, while PKCι signaling in these two major lung cancer subtypes shares some common elements, it also drives distinct, sub-type specific pathways. Furthermore, recent analysis has revealed both PKCι-dependent and PKCι-independent pathways to LADC development. Herein, we discussion our current knowledge of oncogenic PKCι signaling in LADC and LSCC, and discuss these findings in the context of how they may inform strategies for improved therapeutic intervention in these deadly diseases.
蛋白激酶 Cι(PKCι)是一种主要的癌基因,参与多种人类癌症的起始、维持和进展。在肺部,PKCι对于两种主要非小细胞肺癌(NSCLC)——肺腺癌(LADC)和肺鳞状细胞癌(LSCC)的转化表型的维持是必需的。此外,PKCι通过建立和维持高度侵袭性的干细胞样、肿瘤起始细胞表型,对于 LADC 和 LSCC 的肿瘤发生也是必需的。然而,有趣的是,尽管这两种主要肺癌亚型中的 PKCι 信号转导具有一些共同的成分,但它也驱动着不同的、亚型特异性的途径。此外,最近的分析揭示了 PKCι 依赖性和 PKCι 非依赖性途径对于 LADC 的发展。在此,我们讨论了我们目前对于 LADC 和 LSCC 中致癌性 PKCι 信号转导的认识,并在这些发现的背景下讨论了它们如何为改善这些致命疾病的治疗干预策略提供信息。