2. Academic Validation
  3. ISX promotes tumor migration and invasion in lung cancer by upregulating COL1A1 in vitro

ISX promotes tumor migration and invasion in lung cancer by upregulating COL1A1 in vitro

  • Mol Med Rep. 2026 Feb;33(2):77. doi: 10.3892/mmr.2025.13787.
Yihe Ma # 1,  Ye Chen # 2,  Yuhui Liang # 3,  Yun Huang 1,  Miao Gong 1,  Lifeng Tian 1,  Xiaojun Xiao 3,  Jingyan Liu 4,  Qinmiao Huang 1
Affiliations

Affiliations

  • 1 Department of Respiratory Medicine and Allergy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, Guangdong 518000, P.R. China.
  • 2 Department of Pediatric Medicine, Shenzhen Nanshan People's Hospital, Shenzhen, Guangdong 518000, P.R. China.
  • 3 Shenzhen Key Laboratory of Allergy and Immunology, State Key Laboratory of Respiratory Disease Shenzhen University Division, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China.
  • 4 Emergency Department, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Longgang District People's Hospital of Shenzhen, Shenzhen, Guangdong 518100, P.R. China.
  • # Contributed equally.
PMID: 41480691 DOI: 10.3892/mmr.2025.13787
Abstract

Recurrence and metastasis are the leading causes of poor prognosis and death in lung Cancer, and the mechanism of Cancer metastasis has not yet been fully elucidated. As a gut-specific homeobox (HOX) transcription factor, intestine-specific HOX (ISX) is a proto-oncogene induced by the inflammatory factor IL-6. Notably, ISX overexpression can induce the epithelial-mesenchymal transition (EMT) response, and promotes tumor cell migration and invasion. In the present study, a lung Cancer cell model with overexpression of ISX was established by infecting lung Cancer cells with lentivirus. Reverse transcription-quantitative polymerase chain reaction was first used to verify the expression of the EMT-related gene induced by ISX overexpression. Furthermore, transcriptome Sequencing and analysis showed that the overexpression of ISX induced significant changes in the gene expression profile of human lung Cancer cells. In addition, type I Collagen α1 chain (COL1A1), a highly expressed gene in various tumor tissues and cells, was shown to promote tumor cell migration and invasion, possibly by promoting EMT, and was significantly upregulated in human lung Cancer cells overexpressing ISX. These results suggested that ISX may promote lung Cancer migration and invasion by increasing the expression of COL1A1. In addition, four drugs that are currently used to treat lung Cancer were screened. Of these, Iressa® (gefitinib) was revealed to significantly inhibit the viability, migration and invasion of lung Cancer cells that stably overexpress ISX by downregulating the expression of COL1A1. In conclusion, these findings may help to prevent tumor metastasis and spread, and the potential molecular mechanism by which ISX promotes the development and migration of lung Cancer was suggested. The current findings provide novel targets, and a scientific basis for the prevention and treatment of lung Cancer, which may reduce costs for patients, their families and society.

Keywords

intestine-specific homeobox; invasion; lung cancer; migration; type I collagen α1 chain.

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