ArticleInternational journal of biological sciences2018
CCL2-SQSTM1 positive feedback loop suppresses autophagy to promote chemoresistance in gastric cancer.
Article in International journal of biological sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Prognostic significance of pre-intervention circulating cytokines in digestive system cancers: a systematic review and meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Autophagy as a therapeutic target for cisplatin-resistant gastric cancer.Genes & diseases · 2026Review
- Advances in protein microarray-based proteomics for gastric cancer applications in biomarker discovery, molecular subtyping, and precision oncology.Frontiers in oncology · 2026Review
- FTO-Mediated m6A Demethylation of CCL2 Promotes Gastric Cancer Progression via Autophagy and Oxidative Stress Regulation.Digestive diseases and sciences · 2025Article
- Nutrients Lowering Obesity-Linked Chemokines Blamable for Metastasis.International journal of molecular sciences · 2025Review
- Liquid-liquid phase separation: an emerging perspective on the tumorigenesis, progression, and treatment of tumors.Frontiers in immunology · 2025Review
- NXPH4 mediated by mCellular & molecular biology letters · 2024Article
- CCL2 promotes EGFR-TKIs resistance in non-small cell lung cancer via the AKT-EMT pathway.Acta biochimica et biophysica Sinica · 2024Article
- Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors.International journal of nanomedicine · 2024Review
- Identification of the CCL2 PI3K/Akt axis involved in autophagy and apoptosis after spinal cord injury.Metabolic brain disease · 2023Article
- Dynamic bioinspired coculture model for probing ERScience advances · 2023Article
- Tumors of the Digestive System: Comprehensive Review of Ancillary Testing and Biomarkers in the Era of Precision Medicine.Current oncology (Toronto, Ont.) · 2023Review
- Review
- Review
- Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation.Frontiers in cardiovascular medicine · 2022Article
- Mechanism of Herb PairsEvidence-based complementary and alternative medicine : eCAM · 2022Article
- The Role of Lipid Metabolism in Gastric Cancer.Frontiers in oncology · 2022Review
- Role of the CCL2-CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting.Cell proliferation · 2021Review
- Research advances of secretory proteins in malignant tumors.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy is one of the most important approaches for the treatment of various cancers. However, tumor cells often develop resistance to chemotherapeutic drugs. The tumor microenvironment reconstituted by various cytokines secreted from immune cells was recently found to play important roles in affecting therapeutic response of tumor cells. Herein, we reported that tumor cells can secrete autocrine cytokines to confer chemoresistance by inactivating proapoptotic autophagy. Through cytokine screening, we found that drug resistant cancer cells secreted more CCL2 than drug sensitive cells. Such secreted CCL2 could not only maintain chemoresistance in drug-resistant cancer cells but also confer drug resistance to drug-sensitive cancer cells. CCL2 attenuated drug-induced cytotoxicity by activating PI3K-Akt-mTOR signaling to inhibit proapoptotic autophagy and increase SQSTM1 expression. CCL2 expression in primary carcinoma tissues also correlated well with SQSTM1 expression. Either CCL2 knock-down or autophagy induction successfully reversed drug resistance of tumor cells. Moreover, increased expression of SQSTM1 in turn activated CCL2 transcription via NF-κB signal pathway, representing a positive feedback loop to maintain drug resistance. Therefore, our results provided a new insight to understand drug resistance, and indicated the potential value of CCL2 as a biomarker and intervention target for chemotherapy resistance.
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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 Socratic graph.