Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Hunan Province, Changsha 410008, China.
Key Laboratory of Molecular Radiation Oncology Hunan Province, Hunan Province, Changsha 410008, China.
Int J Biol Sci. 2023 Jun 19;19(10):3184-3199. doi: 10.7150/ijbs.84322. eCollection 2023.
Metastasis is a significant cause of high mortality in lung cancer. Lymph node (LN) metastasis is the most common metastatic pathway in non-small cell lung cancer and the most crucial factor affecting the prognosis of NSCLC. Nevertheless, the molecular mechanism underlying metastasis is unknown. We demonstrated that higher NADK expression suggests worsened survival prognosis, and NADK expression positively correlates with the lymph node metastasis rate and TNM and AJCC stages in NSCLC patients. Moreover, patients with LN metastasis show higher NADK expression than those without LN metastasis. NADK can promote NSCLC progression by enhancing the migration, invasion, lymph node metastasis and growth of NSCLC cells. Mechanistically, NADK inhibits the ubiquitination and degradation of BMPR1A by interacting with Smurf1, further activating the BMPs signalling pathway and promoting ID1 transcription. In conclusion, NADK may be a potential diagnostic indicator and a novel therapeutic target for metastatic NSCLC.
转移是肺癌高死亡率的重要原因。淋巴结（LN）转移是非小细胞肺癌最常见的转移途径，也是影响 NSCLC 预后的最关键因素。然而，转移的分子机制尚不清楚。我们发现 NADK 表达水平越高，患者的生存预后越差，且 NADK 表达与 NSCLC 患者的淋巴结转移率、TNM 和 AJCC 分期呈正相关。此外，有淋巴结转移的患者 NADK 表达高于无淋巴结转移的患者。NADK 可通过增强 NSCLC 细胞的迁移、侵袭、淋巴结转移和生长来促进 NSCLC 的进展。在机制上，NADK 通过与 Smurf1 相互作用抑制 BMPR1A 的泛素化和降解，进而激活 BMPs 信号通路并促进 ID1 转录。总之，NADK 可能是转移性 NSCLC 的一个有潜力的诊断指标和新的治疗靶点。
