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Extracellular AGR2 ...
Extracellular AGR2 activates neighboring fibroblasts through endocytosis and direct binding to β-catenin that requires AGR2 dimerization and adhesion domains
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- Merugu, Siva Bharath (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Zhou, Bingjie (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China; Chinese Acad Sci, Univ Chinese Acad Sci, Inst Pasteur Shanghai, CAS Key Lab Mol Virol & Immunol, Shanghai, Peoples R China
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- Mangukiya, Hitesh Bhagavanbhai (author)
- Uppsala universitet,Neuroonkologi,Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Negi, Hema (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Ghulam, Raza (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Roy, Debmalya (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Qudsia, Sehar (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Wang, Zeling (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Mashausi, Dhahiri Saidi (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Yunus, Fakhar-Un-Nisa (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Liu, Guo-Song (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China
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- Li, Dawei (author)
- Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China; Minist Educ, Engn Res Ctr Cell & Therapeut Antibody, Shanghai, Peoples R China
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(creator_code:org_t)
- Elsevier, 2021
- 2021
- English.
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In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 573, s. 86-92
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Anterior gradient 2 (AGR2) is often overexpressed in several types of cancer. AGR2 is cytoplasmic or secreted as an extracellular signal. Intracellular AGR2 properties and role in cancer have been well studied, but its extracellular function is largely unclear. It has been shown that extracellular AGR2 activates endothelial cells and fibroblasts in culture, but the mechanism of AGR2 signaling is not well elucidated. Here, we report that tumor secreted or externally added AGR2 translocates into cytoplasm by endocytosis, binds to β-catenin and further co-translocates to the nucleus in NIH3T3 fibroblasts. Externally added AGR2 also increased β-catenin expression, stability, and accumulation in the nucleus in both fibroblasts and cancer cells. External AGR2 rescued the expression of β-catenin, which was suppressed by EGFR inhibitor AG1478 indicating an alternative pathway to regulate β-catenin independent of EGFR signal. These effects were abolished when a monoclonal antibody against AGR2 was added to the experiments, confirming the effects are caused by AGR2 only. Putting together, our results show that extracellular AGR2 signaling pathway involves endocytosis mediated cellular translocation, direct binding and regulating β-catenin nuclear accumulation. It is also a target against tumor initiated AGR2 signaling to form and maintain tumor microenvironment.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Extracellular AGR2
- Tumor microenvironment
- Fibroblasts
- beta-catenin
- 18A4
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Merugu, Siva Bha ...
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Zhou, Bingjie
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Mangukiya, Hites ...
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Negi, Hema
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Ghulam, Raza
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Roy, Debmalya
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show more...
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Qudsia, Sehar
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Wang, Zeling
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Mashausi, Dhahir ...
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Yunus, Fakhar-Un ...
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Liu, Guo-Song
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Li, Dawei
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Biochemical and ...
- By the university
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Uppsala University