Ahn Hye-Mi, Choi Eun-Young, Kim Youn-Jae
Targeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi, Korea.
Cancers (Basel). 2021 Dec 21;14(1):19. doi: 10.3390/cancers14010019.
Lung adenocarcinoma is one of the leading causes of cancer-related deaths. Despite the availability of advanced anticancer drugs for lung cancer treatment, the prognosis of patients still remains poor. There is a need to explore novel oncogenic mechanisms to overcome these therapeutic limitations. The functional experiments in vitro and in vivo were performed to evaluate the role of GPR87 expression on lung adenocarcinoma metastasis. The public lung adenocarcinoma dataset was used to determine the clinical relevance of GPR87 expression in patients with lung adenocarcinoma. GPR87 is upregulated in various cancer; however, the biological function of GPR87 has not yet been established in lung adenocarcinoma. In this study, we found that GPR87 expression is upregulated in lung adenocarcinoma and is associated with poor patient prognosis. Additionally, we showed that GPR87 overexpression promotes invasiveness and metastasis of lung adenocarcinoma cells. Furthermore, we demonstrated that AKT-eNOS-NO signaling is a novel downstream pathway of GPR87 in lung adenocarcinoma. Conversely, we confirmed that silencing of GPR87 expression suppressed these phenotypes. Our results reveal the oncogenic function of GPR87 in cancer progression and metastasis through the activation of eNOS as a key mediator. Therefore, we propose that targeting eNOS could be a novel therapeutic strategy to improve the clinical treatment of lung adenocarcinoma.
肺腺癌是癌症相关死亡的主要原因之一。尽管有先进的抗癌药物可用于肺癌治疗，但患者的预后仍然很差。有必要探索新的致癌机制以克服这些治疗局限性。进行了体外和体内功能实验，以评估GPR87表达对肺腺癌转移的作用。使用公开的肺腺癌数据集来确定GPR87表达在肺腺癌患者中的临床相关性。GPR87在各种癌症中上调；然而，GPR87在肺腺癌中的生物学功能尚未确定。在本研究中，我们发现GPR87在肺腺癌中表达上调，且与患者预后不良相关。此外，我们表明GPR87过表达促进肺腺癌细胞的侵袭和转移。此外，我们证明AKT-eNOS-NO信号通路是肺腺癌中GPR87的一条新的下游通路。相反，我们证实沉默GPR87表达可抑制这些表型。我们的结果揭示了GPR87通过激活作为关键介质的eNOS在癌症进展和转移中的致癌功能。因此，我们提出靶向eNOS可能是改善肺腺癌临床治疗的一种新的治疗策略。
