ArticleCancer science2018
Collagen type I induces EGFR-TKI resistance in EGFR-mutated cancer cells by mTOR activation through Akt-independent pathway.
Article in Cancer science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Mitochondrial niches of residual disease in EGFR-mutant NSCLC: immune-constrained persistence and therapeutic interception.Frontiers in immunology · 2026Review
- Deciphering context-specific Axitinib escape pathways via multi-omics and explainable machine learning.Journal of translational medicine · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Dickkopf-1 promotes tumor progression of gefitinib- resistant non-small cell lung cancer through cancer cell-fibroblast interactions.Experimental hematology & oncology · 2025Article
- Targeting the Tumor Microenvironment in EGFR-Mutant Lung Cancer: Opportunities and Challenges.Biomedicines · 2025Review
- Overcoming EGFR-TKI resistance by targeting the tumor microenvironment.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Lactate-driven type I collagen deposition facilitates cancer stem cell-like phenotype of head and neck squamous cell carcinoma.iScience · 2024Article
- Plumbagin as a preferential lead molecule to combat EGFR-driven matrix abundance and migration of cervical carcinoma cells.Medical oncology (Northwood, London, England) · 2024Article
- ELK1/MTOR/S6K1 Pathway Contributes to Acquired Resistance to Gefitinib in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Article
- Cancer-associated fibroblast-dependent and -independent invasion of gastric cancer cells.Journal of cancer research and clinical oncology · 2023Article
- Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression.BMC complementary medicine and therapies · 2023Article
- Systematic pan-cancer analysis of the potential tumor diagnosis and prognosis biomarker P4HA3.Frontiers in genetics · 2023Article
- COL3A1 Overexpression Associates with Poor Prognosis and Cisplatin Resistance in Lung CancerBalkan medical journal · 2022Article
- The importance of being CAFs (in cancer resistance to targeted therapies).Journal of experimental & clinical cancer research : CR · 2022Review
- Smoking-associated Downregulation of FILIP1L Enhances Lung Adenocarcinoma Progression Through Mucin Production, Inflammation, and Fibrosis.Cancer research communications · 2022Article
- [P4HA2 promotes occurrence and progression of liver cancer by regulating the PI3K/Akt/mTOR signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- 18F-fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma.Cancer science · 2022Article
- mTOR Signaling Components in Tumor Mechanobiology.International journal of molecular sciences · 2022Review
- Review
- The Role and Therapeutic Potential of Macropinocytosis in Cancer.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a serious problem in lung adenocarcinoma patients harboring EGFR mutations. The aim of this study was to examine whether and how collagen type I (Col I), the most abundantly deposited matrix in tumor stroma, affects EGFR-TKI sensitivity in EGFR-mutant cells. We evaluated the EGFR-TKI sensitivity of EGFR-mutated cancer cells cultured with Col I. Changes in the activation of downstream signaling molecules of EGFR were analyzed. We also examined the association between the Col I expression in tumor stroma in surgical specimens and EGFR-TKI response of postoperative recurrence patients with EGFR mutations. Compared to cancer cells without Col I, the survival rate of cancer cells cultured with Col I was significantly higher after EGFR-TKI treatment. In cancer cells cultured with and without Col I, EGFR-TKI suppressed the levels of phosphorylated (p-)EGFR, p-ERK1/2, and p-Akt. When compared to cancer cells without Col I, expression of p-P70S6K, a hallmark of mTOR activation, was dramatically upregulated in cancer cells with Col I. This activation was maintained even after EGFR-TKI treatment. Simultaneous treatment with EGFR-TKI and mTOR inhibitor abrogated Col I-induced resistance to EGFR-TKI. Patients with Col I-rich stroma had a significantly shorter progression-free survival time after EGFR-TKI therapy (238 days vs 404 days; P < .05). Collagen type I induces mTOR activation through an Akt-independent pathway, which results in EGFR-TKI resistance. Combination therapy using EGFR-TKI and mTOR inhibitor could be a possible strategy to combat this resistance.
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