2. Academic Validation
  3. NTRK fusion promotes tumor migration and invasion through epithelial-mesenchymal transition and closely interacts with ECM1 and NOVA1

NTRK fusion promotes tumor migration and invasion through epithelial-mesenchymal transition and closely interacts with ECM1 and NOVA1

  • BMC Cancer. 2024 Dec 5;24(1):1502. doi: 10.1186/s12885-024-13271-w.
Siqing Zeng 1 2 3 4 5,  Ke Jiang 1 2 3 4 5,  Jie Ge 6 5,  Mimi Tang 7,  Yuqi Wen 1 2 3 4 5,  Xiaoting Ma 1 2 3 4 5,  Heli Liu 8 9,  Xingui Xiong 10 11 12 13 14
Affiliations

Affiliations

  • 1 Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
  • 2 NATCM Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
  • 3 Hunan Key Laboratory of TCM GanXiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
  • 4 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
  • 5 Project Funded By The Leading National Joint Discipline Of Chinese And Western Medicines To The Chinese Medicine Department, Xiangya Hospital, CSU, Changsha, China.
  • 6 Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
  • 7 Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
  • 8 Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. heliliu@csu.edu.cn.
  • 9 Project Funded By The Leading National Joint Discipline Of Chinese And Western Medicines To The Chinese Medicine Department, Xiangya Hospital, CSU, Changsha, China. heliliu@csu.edu.cn.
  • 10 Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. xiongxg07@csu.edu.cn.
  • 11 NATCM Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. xiongxg07@csu.edu.cn.
  • 12 Hunan Key Laboratory of TCM GanXiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. xiongxg07@csu.edu.cn.
  • 13 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China. xiongxg07@csu.edu.cn.
  • 14 Project Funded By The Leading National Joint Discipline Of Chinese And Western Medicines To The Chinese Medicine Department, Xiangya Hospital, CSU, Changsha, China. xiongxg07@csu.edu.cn.
PMID: 39639242 DOI: 10.1186/s12885-024-13271-w
Abstract

Background: The NTRK fusion gene is a rare Cancer driver and a typical representative "diamond mutation". Its unique role in tumor progression is highly important for the clinical diagnosis and treatment of patients with tumors. We searched for NTRK fusion-positive patients in our hospital. As of August 2022, a total of 8 patients were affected. We discovered that NTRK fusion was associated with enhanced tumor invasion and migration ability. Previous reports also support this finding, but its underlying mechanism has not been elucidated.

Methods: We undertook a comprehensive exploration of the correlations between NTRK fusions and tumor invasion as well as migration by analysing clinical data, performing bioinformatics analysis via public databases, and conducting in vitro cell experiments.

Results: We ascertained that within the thyroid Cancer (THCA) dataset and the pancancer dataset, ECM1 and NOVA1 were coexpressed with NTRKs. Additionally, they demonstrated a significant association with the activity of the epithelial‒mesenchymal transition (EMT) pathway. Furthermore, these genes are overexpressed in various cancers and are associated with advanced clinical stage and increased aggressiveness. Our in vitro study revealed that larolutinib potentially inhibited the invasion and metastasis ability of NTRK-fused cells. Interestingly, contrary to previous findings, the repression of ECM1 increased the migration and invasion ability of NTRK-fused tumor cells.

Conclusions: NTRK fusion tumors present heightened migratory and invasive potential in clinical settings. Further experiments confirmed the significant inhibitory effects of Trk inhibitors on the migration and invasion abilities of these cells. There is a complex relationship between ECM1, NOVA1 and NTRK fusion; however, further research is needed to determine whether NTRK fusion promotes tumor metastasis through these two genes.

Keywords

Cancer; ECM1; EMT; NTRK fusion; TRK inhibitor.

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