High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population

Lin, Yingsong; Long, Huidong; Chen, Cheng-Cong; Liu, Guancheng; Li, Feng; Tian, Yunhong; Dai, Lu

doi:10.21037/jtd-22-1523

Cited by 2 publications

(1 citation statement)

References 43 publications

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“…4f, g). Phosphorylation of FGFR3, an RTK recently reported to be highly expressed in NSCLC samples 42 but not FGFR1 was induced in S-AlgLung hydrogels. Interestingly, phosphorylated EGFR was even reduced in sulfated gels (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 86%

Extracellular matrix sulfation in the tumor microenvironment stimulates cancer stemness and invasiveness

Kuşoğlu,

Örnek,

Dansık

et al. 2023

Preprint

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Tumor extracellular matrices (ECM) exhibit aberrant changes in composition and mechanics compared to normal tissues. Proteoglycans (PG) are vital regulators of cellular signaling in the ECM with ability to modulate receptor tyrosine kinase (RTK) activation via their sulfated glycosaminoglycan (sGAG) side chains. However, their role on tumor cell behavior is controversial. Here, we demonstrate that PGs are heavily expressed in lung adenocarcinoma patients in correlation with invasive phenotype and poor prognosis. We developed a bioengineered human lung tumor model which recapitulates the increase of sGAGs in tumors in an organotypic matrix with independent control of stiffness, viscoelasticity, ligand density and porosity. Our model reveals that increased sulfation stimulates extensive proliferation, epithelial-mesenchymal transition and stemness in cancer cells. We identified the FAK-PI3K-mTOR signaling axis as a mediator of sulfation-induced molecular changes in cells upon activation of a distinct set of RTKs within tumor-mimetic hydrogels. We demonstrate that the transcriptomic landscape of tumor cells in response to increased sulfation resembles native PG-rich patient tumors through employing integrative omics and network modeling approaches.

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Section: Resultsmentioning

confidence: 86%

Extracellular matrix sulfation in the tumor microenvironment stimulates cancer stemness and invasiveness

Kuşoğlu,

Örnek,

Dansık

et al. 2023

Preprint

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Regulatory mechanism of the Glabrene against non‐small cell lung cancer by suppressing FGFR3

He,

Wu,

et al. 2024

Environmental Toxicology

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BackgroundNon‐small cell lung cancer (NSCLC) is a highly malignant tumor with limited effective treatment options. This study aimed to investigate the regulatory mechanism of Glabrene on NSCLC through its interaction with FGFR3.MethodsHCC827 cells were implanted into nude mice and treated with Glabrene. Tumor volume was monitored at 0, 3, 6, and 9 days after medical treatment. Tissue analysis included Hematoxylin and Eosin (HE) and Terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP Nick End Labeling (TUNEL) staining, as well as immunohistochemistry for Ki67, ERK1/2, and p‐ERK1/2 expression. Cell viability was determined with the CCK8 method. We utilized immunofluorescence techniques to observe apoptosis, as well as the levels of E‐cadherin and Vimentin expression. Cellular proliferation was determined via plate cloning assay and cellular mobility was determined via scratch assay. Cellular invasion ability was assessed via a transwell assay. mRNA and protein levels of FGFR3, MMP1, MMP9, vimentin, E‐cadherin, ERK1/2, and p‐ERK1/2 were detected via qPCR and Western blot. IGF‐1, VEGF, and Estradiol (E2) levels were measured through Enzyme linked immunosorbent assay (ELISA).ResultsThis study verified that Glabrene was capable of suppressing tumor growth in NSCLC mice, reversing tumor tissue's pathological morphology, attenuating the capacities of cancerous cells' proliferation, migration, and invasion, and leading to apoptosis. Besides, Glabrene could reduce the FGFR3 expression in HCC827 cells. Over‐expression of FGFR3 promotes the proliferation of HCC827 cells, increase both contents of IGF‐1, VEGF, and E2, and expressions of MMP1, MMP9, vimentin, and p‐ERK1/2, while Glabrene inhibited FGFR3. Glabrene, and inhibition of FGFR3 expression were capable of decreasing FGFR3, MMP1, MMP9, vimentin, and p‐ERK1/2 expression, as well as contents of IGF‐1, VEGF, and E2 in model mice and HCC827 cells, and promoting the expression of E‐cadherin.ConclusionGlabrene has the potential as a therapeutic agent for NSCLC by reducing cancer invasion and migration through the inhibition of ERK1/2 phosphorylation and suppression of epithelial‐mesenchymal transition (EMT).

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High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population

Cited by 2 publications

References 43 publications

Extracellular matrix sulfation in the tumor microenvironment stimulates cancer stemness and invasiveness

Extracellular matrix sulfation in the tumor microenvironment stimulates cancer stemness and invasiveness

Regulatory mechanism of the Glabrene against non‐small cell lung cancer by suppressing FGFR3

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