ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
Clathrin mediates endocytosis of progastrin and activates MAPKs: role of cell surface annexin A2.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Progastrin, annexin A2, and tumor-associated macrophages in gastric adenocarcinoma.Journal of pathology and translational medicine · 2026Article
- Osteocalcin induces phosphorylation of FOXO1 in human beta-cells and restores insulin expression under hyperglycemic conditions.Research square · 2025Article
- Review
- Elevated Serum Gastrin Is Associated with Melanoma Progression: Putative Role in Increased Migration and Invasion of Melanoma Cells.International journal of molecular sciences · 2023Article
- Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2.World journal of gastroenterology · 2015Review
- Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach for diagnosis of colon cancer relapse/metastasis.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Novel roles of gastrin.The Journal of physiology · 2014Review
- Cationic lipid guided short-hairpin RNA interference of annexin A2 attenuates tumor growth and metastasis in a mouse lung cancer stem cell model.Journal of controlled release : official journal of the Controlled Release Society · 2014Article
- A network map of the gastrin signaling pathway.Journal of cell communication and signaling · 2014Article
- Progastrin-induced secretion of insulin-like growth factor 2 from colonic myofibroblasts stimulates colonic epithelial proliferation in mice.Gastroenterology · 2013Article
- Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Annexin A2 heterotetramer: structure and function.International journal of molecular sciences · 2013Article
- Domains I and IV of annexin A2 affect the formation and integrity of in vitro capillary-like networks.PloS one · 2013Article
- Gastrin receptor pharmacology.Current gastroenterology reports · 2012Article
- Progastrin Peptides Increase the Risk of Developing Colonic Tumors: Impact on Colonic Stem Cells.Current colorectal cancer reports · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cell-surface-associated annexin A2 (CS-ANXA2) is a nonconventional "receptor" for progastrin; expression levels of both are elevated in colon cancers, and downregulation of either reduces tumorigenic potential of cells. We recently reported internalization of progastrin in target cells. Here, mechanisms mediating internalization of progastrin were examined. Initially, we confirmed that cell-surface ANXA2 mediates binding and internalization of progastrin in intestinal cells. Progastrin, covalently linked to sepharose beads, failed to activate p38MAPK/ERKs, suggesting internalization of progastrin was required for eliciting biological effects; importantly annexin A2 expression and availability of CS-ANXA2 were required for internalization of progastrin. Clathrin expression and formation of clathrin-coated pits were critically required for endocytotic internalization of progastrin; in the absence of clathrin, progastrin failed to activate p38MAPK/ERKs. Downregulation of caveolin had no effect on binding or internalization of progastrin. We therefore demonstrate for the first time that progastrin binds CS-ANXA2 and is rapidly internalized via clathrin-mediated endocytotic pathway, resulting in activation of MAPKinases. Targeting clathrin-mediated endocytosis of progastrin may thus inhibit previously reported co-carcinogenic/tumorigenic effects of progastrin on intestinal cells.
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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.