The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
The Epidermal Growth Factor Receptor Antibody Cetuximab Induces Autophagy in Cancer Cells by Downregulating HIF-1α and Bcl-2 and Activating the Beclin 1/hVps34 Complex
Open accessAbstract
Autophagy is a regulated catabolic process triggered in cells deprived of nutrients or growth factors that govern nutrient uptake. Here, we report that autophagy is induced by cetuximab, a therapeutic antibody that blocks epidermal growth factor receptor function. Cancer cell treatment with cetuximab triggered autophagosome formation, conversion of microtubule-associated protein 1 light chain 3 from its cytoplasmic to membrane-associated form, and increased acidic vesicular organelle formation. Autophagy occurred when cetuximab inhibited the class I phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin pathway, but not when it inhibited only the mitogen-activated protein/extracellular signal-regulated kinase kinase/Erk pathway, and it was accompanied by decreased levels of hypoxia inducible factor-1 α (HIF-1α) and Bcl-2. Stable overexpression of a HIF-1α mutant prevented cetuximab-induced autophagy and decrease in Bcl-2 levels. Knockdown of autophagy regulator beclin 1 or cell treatment with autophagy inhibitor 3-methyladenine, a class III PI3K (hVps34) inhibitor, also inhibited cetuximab-induced autophagy. Furthermore, knockdown of beclin 1 or Atg7 or treatment with the lysosome inhibitor chloroquine sensitized cancer cells to cetuximab-induced apoptosis. Mechanistic analysis argued that cetuximab acted by promoting an association between beclin 1 and hVps34, which was inhibited by overexpression of Bcl-2. Our findings suggest that the autophagy protects cancer cells from the proapoptotic effects of cetuximab. Cancer Res; 70(14); 5942–52. ©2010 AACR.
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“Autophagy inhibitor, such as chloroquine/3-MA, could enhance the sensitivity of CRC cells to cetuximab-induced cell death [45,46].”
From Drug Resistance in Colorectal Cancer: From Mechanism to Clinic (2022) · cites this paper as [45]
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“Treatment with anti-EGFR agents results in dysregulation of autophagy [138].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [138]
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“Inhibition of autophagy by chloroquine and 3-methyladenine sensitizes cancer cells to cetuximab [138, 139].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [138]
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Metadata
- Authors
- Li, X., & Fan, Z.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Fan, Zhen
- ORCID
- Fan, Zhen
- Venue
- Cancer Research
- Published
- 2010-07-14
- Volume
- 70
- Issue
- 14
- Pages
- 5942-5952
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2933174
- OpenAlex
- W2159809160
- Cited by
- 179
- References
- 51
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 11 · 2019: 8 · 2018: 16 · 2017: 16 · 2016: 18 · 2015: 14 · 2014: 13 · 2013: 18 · 2012: 16
- FWCI
- 11.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- Office of Defense Programs
- National Cancer Institute (CA 016672, R01CA129036, P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- cetuximab, autophagy, epidermal growth factor receptor, HIF-1α, Bcl-2, Beclin-1, PI3K/AKT/mTOR pathway, autophagy-related genes, apoptosis, cancer cells, 3-methyladenine, chloroquine, ATG7
- MeSH terms
- Cetuximab, Beclin-1, Phosphoinositide-3 Kinase Inhibitors, Adenocarcinoma, Antibodies, Monoclonal, Autophagy, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Female, Humans, Lung Neoplasms, Membrane Proteins, Neoplasms, Vulvar Neoplasms, Colorectal Neoplasms, Down-Regulation, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins c-bcl-2, Phosphatidylinositol 3-Kinases, MAP Kinase Kinase Kinases, Vesicular Transport Proteins, Intracellular Signaling Peptides and Proteins, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases, Antibodies, Monoclonal, Humanized, ErbB Receptors
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