Lung cancer (LC) has the highest relative risk of development as a comorbidity of chronic obstructive pulmonary disease (COPD). The molecular mechanisms that mediate chronic inflammation and lung function impairment in COPD have been identified in LC. This suggests the two diseases are more linked than once thought. Emerging data in relation to a key phosphatase, protein phosphatase 2A (PP2A), and its regulatory role in inflammatory and tumour suppression in both disease settings suggests that it may be critical in the progression of COPD to LC. In this review, we uncover the importance of the functional and active PP2A holoenzyme in the context of both diseases. We describe PP2A inactivation via direct and indirect means and explore the actions of two key PP2A endogenous inhibitors, cancerous inhibitor of PP2A (CIP2A) and inhibitor 2 of PP2A (SET), and the role they play in COPD and LC. We explain how dysregulation of PP2A in COPD creates a favourable inflammatory micro-environment and promotes the initiation and progression of tumour pathogenesis. Finally, we highlight PP2A as a druggable target in the treatment of COPD and LC and demonstrate the potential of PP2A re-activation as a strategy to halt COPD disease progression to LC. Although further studies are required to elucidate if PP2A activity in COPD is a causal link for LC progression, studies focused on the potential of PP2A reactivating agents to reduce the risk of LC formation in COPD patients will be pivotal in improving clinical outcomes for both COPD and LC patients in the future.

中文翻译：

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蛋白磷酸酶 2A (PP2A)：慢性阻塞性肺疾病 (COPD) 进展为肺癌的关键磷酸酶

作为慢性阻塞性肺病 (COPD) 的合并症，肺癌 (LC) 的相对风险最高。慢性阻塞性肺病 (COPD) 中介导慢性炎症和肺功能损伤的分子机制已在 LC 中得到确定。这表明这两种疾病之间的联系比以前想象的更为密切。与关键磷酸酶、蛋白磷酸酶 2A (PP2A) 相关的新数据及其在两种疾病中炎症和肿瘤抑制中的调节作用表明，它可能在 COPD 进展为 LC 的过程中发挥关键作用。在这篇综述中，我们揭示了功能性和活性 PP2A 全酶在这两种疾病中的重要性。我们通过直接和间接方式描述了 PP2A 失活，并探讨了两种关键 PP2A 内源性抑制剂：癌性 PP2A 抑制剂 (CIP2A) 和 PP2A 抑制剂 2 (SET) 的作用，以及它们在 COPD 和 LC 中的作用。我们解释了 COPD 中 PP2A 的失调如何创造有利的炎症微环境并促进肿瘤发病机制的启动和进展。最后，我们强调 PP2A 作为治疗 COPD 和 LC 的药物靶标，并证明 PP2A 重新激活作为阻止 COPD 疾病进展为 LC 的策略的潜力。尽管需要进一步的研究来阐明 COPD 中的 PP2A 活性是否是 LC 进展的因果关系，但针对 PP2A 重新激活剂降低 COPD 患者中 LC 形成风险的潜力的研究对于改善 COPD 和 LC 的临床结果至关重要。未来的 LC 患者。