ArticleNPJ precision oncology2022
Activation of CD44/PAK1/AKT signaling promotes resistance to FGFR1 inhibition in squamous-cell lung cancer.
Article in NPJ precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- ATF6-mediated GTPase RHOQ promotes liver cancer progression via enhancing aerobic glycolysis through PAK1 phosphorylation.Clinical and translational medicine · 2026Article
- Targeting PAK1 suppresses tumor progression by promoting mRNA decay of oncogenic factors and enhancing chemotherapeutic efficacy in colorectal cancer.Genes & diseases · 2026Article
- SPP1 promotes cancer stemness and reduces osimertinib sensitivity in non-small cell lung cancer through interactions with CD44.Cancer cell international · 2026Article
- Protein kinase B inhibitors enhance the sensitivity of translocated promoter region-fibroblast growth factor receptor 1 cells to fibroblast growth factor receptor 1 inhibitor-induced apoptosis.The Journal of international medical research · 2025Article
- Moesin silencing enhances the radiosensitivity of glioblastoma by inhibiting DNA damage repair via CD44/AKT1 signaling pathway.Discover oncology · 2025Article
- Article
- MTHFD2 marks pemetrexed resistance in pulmonary adenocarcinoma with EGFR wild type.Discover oncology · 2025Article
- A novel PAK1/TCF1 regulatory axis promotes non-small cell lung cancer progression.Discover oncology · 2025Article
- β-sitosterol suppresses fibroblast growth factor and epidermal growth factor receptors to induce apoptosis and inhibit migration in lung cancer: an in vitro study.American journal of cancer research · 2025Article
- Targeting ErbB and tankyrase1/2 prevent the emergence of drug-tolerant persister cells in ALK-positive lung cancer.NPJ precision oncology · 2024Article
- Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria-related pathways in colorectal cancer.Molecular oncology · 2024Article
- Activation of the mTOR pathway promotes neurite growth through upregulation of CD44 expression.The Journal of international medical research · 2023Article
- A systematic and comprehensive analysis of T cell exhaustion related to therapy in lung adenocarcinoma tumor microenvironment.Frontiers in pharmacology · 2023Article
- RNA-binding proteins regulating the CD44 alternative splicing.Frontiers in molecular biosciences · 2023Review
- [Update thoracic pathology 2022-Report of the Thoracic Pathology Working Group of the German Society of Pathology].Pathologie (Heidelberg, Germany) · 2022Article
- FGF1 protects FGFR1-overexpressing cancer cells against drugs targeting tubulin polymerization by activating AKTFrontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. Fibroblast growth factor receptor 1 (FGFR1) gene amplification is one of the most prominent and potentially targetable genetic alterations in squamous-cell lung cancer (SQCLC). Highly selective tyrosine kinase inhibitors have been developed to target FGFR1; however, resistance mechanisms originally existing in patients or acquired during treatment have so far led to limited treatment efficiency in clinical trials. In this study we performed a wide-scale phosphoproteomic mass-spectrometry analysis to explore signaling pathways that lead to resistance toward FGFR1 inhibition in lung cancer cells that display (i) intrinsic, (ii) pharmacologically induced and (iii) mutationally induced resistance. Additionally, we correlated AKT activation to CD44 expression in 175 lung cancer patient samples. We identified a CD44/PAK1/AKT signaling axis as a commonly occurring resistance mechanism to FGFR1 inhibition in lung cancer. Co-inhibition of AKT/FGFR1, CD44/FGFR1 or PAK1/FGFR1 sensitized 'intrinsically resistant' and 'induced-resistant' lung-cancer cells synergetically to FGFR1 inhibition. Furthermore, strong CD44 expression was significantly correlated with AKT activation in SQCLC patients. Collectively, our phosphoproteomic analysis of lung-cancer cells resistant to FGFR1 inhibitor provides a large data library of resistance-associated phosphorylation patterns and leads to the proposal of a common resistance pathway comprising CD44, PAK1 and AKT activation. Examination of CD44/PAK1/AKT activation could help to predict response to FGFR1 inhibition. Moreover, combination between AKT and FGFR1 inhibitors may pave the way for an effective therapy of patients with treatment-resistant FGFR1-dependent lung cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.