ArticleAutophagy2015
The epithelial polarity regulator LGALS9/galectin-9 induces fatal frustrated autophagy in KRAS mutant colon carcinoma that depends on elevated basal autophagic flux.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- The Galectin Family in Colorectal Cancer: Integrating Molecular Mechanisms with Diagnostic, Prognostic, and Therapeutic Perspectives.Biomedicines · 2026Review
- Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025Review
- Galectin-9 treatment is cytotoxic for B cell lymphoma by disrupting autophagy.Frontiers in pharmacology · 2025Article
- Decoding the hypoxic tumor microenvironment in colorectal cancer for prognostic modeling and therapeutic target discovery.Frontiers in immunology · 2025Article
- Exploring MPC1 as a potential ferroptosis-linked biomarker in the cervical cancer tumor microenvironment: a comprehensive analysis.BMC cancer · 2024Article
- Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma.Frontiers in immunology · 2024Review
- A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9).Genes & diseases · 2023Review
- Galectin-9 has non-apoptotic cytotoxic activity toward acute myeloid leukemia independent of cytarabine resistance.Cell death discovery · 2023Article
- Galectins and galectin-mediated autophagy regulation: new insights into targeted cancer therapy.Biomarker research · 2023Review
- Galectin-9 in cancer therapy: from immune checkpoint ligand to promising therapeutic target.Frontiers in cell and developmental biology · 2023Review
- Galectin functions in cancer-associated inflammation and thrombosis.Frontiers in cardiovascular medicine · 2023Review
- Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity.Biomedicines · 2021Article
- TRIM39 deficiency inhibits tumor progression and autophagic flux in colorectal cancer via suppressing the activity of Rab7.Cell death & disease · 2021Article
- Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine.International journal of molecular sciences · 2021Article
- Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas.Nature communications · 2020Article
- Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes.International journal of molecular sciences · 2019Article
- The multifaceted role of autophagy in cancer and the microenvironment.Medicinal research reviews · 2019Review
- Targeting Autophagy to Overcome Human Diseases.International journal of molecular sciences · 2019Review
- Galectin-9 Mediates HIV Transcription by Inducing TCR-Dependent ERK Signaling.Frontiers in immunology · 2019Article
- The Tim-3-Galectin-9 Pathway and Its Regulatory Mechanisms in Human Breast Cancer.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic mutation of KRAS (Kirsten rat sarcoma viral oncogene homolog) in colorectal cancer (CRC) confers resistance to both chemotherapy and EGFR (epidermal growth factor receptor)-targeted therapy. We uncovered that KRAS mutant (KRAS(mut)) CRC is uniquely sensitive to treatment with recombinant LGALS9/Galectin-9 (rLGALS9), a recently established regulator of epithelial polarity. Upon treatment of CRC cells, rLGALS9 rapidly internalizes via early- and late-endosomes and accumulates in the lysosomal compartment. Treatment with rLGALS9 is accompanied by induction of frustrated autophagy in KRAS(mut) CRC, but not in CRC with BRAF (B-Raf proto-oncogene, serine/threonine kinase) mutations (BRAF(mut)). In KRAS(mut) CRC, rLGALS9 acts as a lysosomal inhibitor that inhibits autophagosome-lysosome fusion, leading to autophagosome accumulation, excessive lysosomal swelling and cell death. This antitumor activity of rLGALS9 directly correlates with elevated basal autophagic flux in KRAS(mut) cancer cells. Thus, rLGALS9 has potent antitumor activity toward refractory KRAS(mut) CRC cells that may be exploitable for therapeutic use.
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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.