ArticlePloS one2015
Cancer Associated Fibroblast-Derived Hepatocyte Growth Factor Inhibits the Paclitaxel-Induced Apoptosis of Lung Cancer A549 Cells by Up-Regulating the PI3K/Akt and GRP78 Signaling on a Microfluidic Platform.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Advances in Concentration Gradient Generation Approaches in a Microfluidic Device for Toxicity Analysis.Cells · 2022Pooled it
- Uncovering the mechanisms of synergistic drug combinations in non-small cell lung cancer through metagene-based classification.PloS one · 2026Article
- Review
- Cancer-on-a-chip for precision cancer medicine.Lab on a chip · 2025Review
- Review
- GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- Article
- Article
- Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.International journal of molecular sciences · 2024Review
- Microphysiological systems as reliable drug discovery and evaluation tools: Evolution from innovation to maturity.Biomicrofluidics · 2023Review
- Micro-engineering and nano-engineering approaches to investigate tumour ecosystems.Nature reviews. Cancer · 2023Review
- Chemotherapy-induced PDL-1 expression in cancer-associated fibroblasts promotes chemoresistance in NSCLC.Lung cancer (Amsterdam, Netherlands) · 2023Article
- Characterization of 3D-Bioprinted In Vitro Lung Cancer Models Using RNA-Sequencing Techniques.Bioengineering (Basel, Switzerland) · 2023Article
- p‑STAT3 influences doxorubicin and etoposide resistance of A549 cells grown in anOncology reports · 2023Article
- Patient-derived organoids of lung cancer based on organoids-on-a-chip: enhancing clinical and translational applications.Frontiers in bioengineering and biotechnology · 2023Review
- Advanced lung organoids and lung-on-a-chip for cancer research and drug evaluation: a review.Frontiers in bioengineering and biotechnology · 2023Review
- Advances in the Lung Cancer Immunotherapy Approaches.Vaccines · 2022Review
- Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer.Cell communication and signaling : CCS · 2022Article
- Cancer-associated fibroblasts in nonsmall cell lung cancer: From molecular mechanisms to clinical implications.International journal of cancer · 2022Review
- Mechanisms of cancer cell death induction by paclitaxel: an updated review.Apoptosis : an international journal on programmed cell death · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor stroma and growth factors provide a survival environment to tumor cells and can modulate their chemoresistance by dysregulating several signal pathways. In this study, we fabricated a three-dimensional (3D) microfluidic chip using polydimethylsiloxane (PDMS) to investigate the impact of hepatocyte growth factor (HGF) from cancer-associated fibroblasts (CAF) on the Met/PI3K/AKT activation, glucose regulatory protein (GRP78) expression and the paclitaxel-induced A549 cell apoptosis. With a concentration gradient generator, the assembled chip was able to reconstruct a tumor microenvironment in vitro. We found high levels of HGF in the supernatants of CAF and the CAF matrix from the supernatants of activated HFL1 fibroblasts or HGF enhanced the levels of Met, PI3K and AKT phosphorylation and GRP78 expression in A549 cells cultured in a 3D cell chamber, which was abrogated by anti-HGF. Inhibition of Met attenuated the CAF matrix-enhanced PI3K/AKT phosphorylation and GRP78 expression while inhibition of PI3K reduced GRP78 expression, but not Met phosphorylation in A549 cells. Inhibition of GRP78 failed to modulate the CAF matrix-enhanced Met/PI3K/AKT phosphorylation in A549 cells. Furthermore, inhibition of PI3K or GRP78 enhanced spontaneous and paclitaxel-induced A549 cell apoptosis. Moreover, treatment with the CAF matrix inhibited spontaneous and medium or high dose of paclitaxel-induced A549 cell apoptosis. Inhibition of PI3K or GRP78 attenuated the CAF matrix-mediated inhibition on paclitaxel-induced A549 cell apoptosis. Our data indicated that HGF in the CAF matrix activated the Met/PI3K/AKT and up-regulated GRP78 expression, promoting chemoresistance to paclitaxel-mediated apoptosis in A549 cells. Our findings suggest that the microfluidic system may represent an ideal platform for signaling research and drug screening.
Indexed as
Identifiers
What OpenQuestion holds
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.