ArticleNeoplasia (New York, N.Y.)2021
STAT3 contributes to cisplatin resistance, modulating EMT markers, and the mTOR signaling in lung adenocarcinoma.
Article in Neoplasia (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
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- The role of the tumour microenvironment in lung cancer and its therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Extracts fromMarine drugs · 2025Article
- Suppression of JAK2/STAT3 Pathway by Notoginsenoside R1 Reduces Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer.Molecular biotechnology · 2025Article
- CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- p53-regulated SESN1 and SESN2 regulate cell proliferation and cell death through control of STAT3.Cell communication and signaling : CCS · 2025Article
- Re-Sensitization of Resistant Ovarian Cancer SKOV3/CDDP Cells to Cisplatin by Curcumin Pre-Treatment.International journal of molecular sciences · 2025Article
- Review
- The NeuroProtect Formula: A Preventive Approach to AD Targeting the HIF-1/PI3K-AKT Signaling Pathway Evaluated throughCombinatorial chemistry & high throughput screening · 2025Article
- Potentiation of Cisplatin Cytotoxicity in Resistant Ovarian Cancer SKOV3/Cisplatin Cells by Quercetin Pre-Treatment.International journal of molecular sciences · 2023Article
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer.JCI insight · 2022Article
- JAK2-Mediated Phosphorylation of Stress-Induced Phosphoprotein-1 (STIP1) in Human Cells.International journal of molecular sciences · 2022Article
- Ginsenoside Rh4 Suppressed Metastasis of Lung Adenocarcinoma via Inhibiting JAK2/STAT3 Signaling.International journal of molecular sciences · 2022Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is the second leading cause of cancer death worldwide and is strongly associated with cisplatin resistance. The transcription factor signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer cells and coordinates critical cellular processes as survival, self-renewal, and inflammation. In several types of cancer, STAT3 controls the development, immunogenicity, and malignant behavior of tumor cells while it dictates the responsiveness to radio- and chemotherapy. It is known that STAT3 phosphorylation at Ser727 by mechanistic target of rapamycin (mTOR) is necessary for its maximal activation, but the crosstalk between STAT3 and mTOR signaling in cisplatin resistance remains elusive. In this study, using a proteomic approach, we revealed important targets and signaling pathways altered in cisplatin-resistant A549 lung adenocarcinoma cells. STAT3 had increased expression in a resistance context, which can be associated with a poor prognosis. STAT3 knockout (SKO) resulted in a decreased mesenchymal phenotype in A549 cells, observed by clonogenic potential and by the expression of epithelial-mesenchymal transition markers. Importantly, SKO cells did not acquire the mTOR pathway overactivation induced by cisplatin resistance. Consistently, SKO cells were more responsive to mTOR inhibition by rapamycin and presented impairment of the feedback activation loop in Akt. Therefore, rapamycin was even more potent in inhibiting the clonogenic potential in SKO cells and sensitized to cisplatin treatment. Mechanistically, STAT3 partially coordinated the cisplatin resistance phenotype via the mTOR pathway in non-small cell lung cancer. Thus, our findings reveal important targets and highlight the significance of the crosstalk between STAT3 and mTOR signaling in cisplatin resistance. The synergic inhibition of STAT3 and mTOR potentially unveil a potential mechanism of synthetic lethality to be explored for human lung cancer treatment.
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