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Int J Biol Sci 2023; 19(10):3184-3199. doi:10.7150/ijbs.84322 This issue Cite

Research Paper

Nicotinamide adenine dinucleotide kinase promotes lymph node metastasis of NSCLC via activating ID1 expression through BMP pathway

Zimei Zeng^1,2,3*, Jie Gao^1,2,3*, Tao Chen^4,5, Ziyu Zhang^6,7,8,9,10, Mengwei Li^1,2,3, Qi Fan^1,2,3,11, Guoqian Liu^1,2,3, Xuebing Li¹², Zhi Li^1,2,3, Chenxi Zhong¹¹, Feng Yao¹¹, Lunquan Sun^1,2,3✉, Yuezhen Deng^4,5,11✉, Min Li^{6,7,8,9,10✉}

1. Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Hunan Province, Changsha 410008, China.
2. Key Laboratory of Molecular Radiation Oncology Hunan Province, Hunan Province, Changsha 410008, China.
3. Hunan International Science and Technology Collaboration Base of Precision Medicine for Cancer, Hunan Province, Changsha 410008, China.
4. State Key Laboratory of Respiratory Diseases at People's Hospital of Yangjiang, Yangjiang, Guangdong 529500, China.
5. Yangjiang Key Laboratory of Respiratory Disease, People's Hospital of Yangjiang, Yangjiang, Guangdong 529500, China.
6. Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China.
7. Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China.
8. Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
9. Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China.
10. National Clinical Research Center for Geriatric Disorders, Changsha, China.
11. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, Shanghai, China.
12. Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.
* These authors contributed equally to this work.

✉ Corresponding authors: Min Li, E-mail: limin2050edu.cn, Tel:86-0731-84327212; Fax: 86-0731-85838261, Department of Respiratory Medicine, Xiangya Hospital, Central South University, 87th of Xiangya Road, Changsha 410008, China; Yuezhen Deng, E-mail: yuezhendengcom, State Key Laboratory of Respiratory Diseases at People's Hospital of Yangjiang, Yangjiang, Guangdong 529500, China; Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Lunquan Sun, E-mail: lunquansunedu.cn, Tel:86-0731-84327212; Fax: 86-0731-84327212, Xiangya Cancer Center, Xiangya Hospital, Central South University, 87th of Xiangya Road, Changsha 410008, China. More

Abstract

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.

Keywords: Lymph node metastasis, Non-small cell lung cancer (NSCLC), NAD Kinase, BMPs signalling, Inhibitor of differentiation 1.

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