2. Academic Validation
  3. Neurokinin-1 receptor promotes non-small cell lung cancer progression through transactivation of EGFR

Neurokinin-1 receptor promotes non-small cell lung cancer progression through transactivation of EGFR

  • Cell Death Dis. 2022 Jan 10;13(1):41. doi: 10.1038/s41419-021-04485-y.
Xiao-Wei Zhang 1 2 3,  Lin Li 1 2 3,  Wen-Qian Hu 1 2 3,  Ming-Ning Hu 1 2 3,  Yan Tao 4,  Hui Hu 1 2,  Xiao-Kang Miao 2 3,  Wen-Le Yang 2 3,  Qiong Zhu 1,  Ling-Yun Mou 5 6 7
Affiliations

Affiliations

  • 1 School of Life Science Lanzhou University, 222 TianShui South Road, Lanzhou, 730000, P. R. China.
  • 2 Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, P. R. China.
  • 3 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Science, Lanzhou University, Lanzhou, 730000, P. R. China.
  • 4 Key Laboratory of Urological Disease of Gansu Province, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, 730000, P. R. China.
  • 5 School of Life Science Lanzhou University, 222 TianShui South Road, Lanzhou, 730000, P. R. China. muly@lzu.edu.cn.
  • 6 Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, P. R. China. muly@lzu.edu.cn.
  • 7 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Science, Lanzhou University, Lanzhou, 730000, P. R. China. muly@lzu.edu.cn.
PMID: 35013118 DOI: 10.1038/s41419-021-04485-y
Abstract

Despite the great advances in target therapy, lung Cancer remains the top cause of cancer-related death worldwide. G protein-coupled receptor neurokinin-1 (NK1R) is shown to play multiple roles in various cancers; however, the pathological roles and clinical implication in lung Cancer are unclarified. Here we identified NK1R as a significantly upregulated GPCR in the transcriptome and tissue array of human lung Cancer samples, associated with advanced clinical stages and poor prognosis. Notably, NK1R is co-expressed with epidermal growth factor receptor (EGFR) in NSCLC patients' tissues and co-localized in the tumor cells. NK1R can crosstalk with EGFR by interacting with EGFR, transactivating EGFR phosphorylation and regulating the intracellular signaling of ERK1/2 and Akt. Activation of NK1R promotes the proliferation, colony formation, EMT, MMP2/14 expression, and migration of lung Cancer cells. The inhibition of NK1R by selective antagonist aprepitant repressed cell proliferation and migration in vitro. Knockdown of NK1R significantly slowed down the tumor growth in nude mice. The sensitivity of lung Cancer cells to gefitinib/osimertinib is highly increased in the presence of the selective NK1R antagonist aprepitant. Our data suggest that NK1R plays an important role in lung Cancer development through EGFR signaling and the crosstalk between NK1R and EGFR may provide a potential therapeutic target for lung Cancer treatment.

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