The ANXA2/S100A10 Complex-Regulation of the Oncogenic Plasminogen Receptor
Alamelu G Bharadwaj1,2, Emma Kempster1, David M Waisman1,2
1Departments of Pathology, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Biomolecules
|December 24, 2021
Summary
The ANXA2/S100A10 complex (AIIt) acts as a key cell surface plasminogen receptor, regulating plasmin generation crucial for cancer progression. S100A10 shows potential as an oncogenic plasminogen receptor biomarker.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Plasmin generation at the cell surface, initiated by plasminogen binding to receptors, is vital for physiological processes like fibrinolysis and wound healing.
- Cancer cells hijack cell surface plasminogen receptors to promote tumor development, progression, and metastasis.
- S100A10, in complex with annexin A2 (ANXA2) forming the AIIt heterotetramer, is a critical plasminogen receptor.
Purpose of the Study:
- To highlight the ANXA2/S100A10 (AIIt) complex as the quintessential cellular plasminogen receptor.
- To introduce and define 'oncogenic plasminogen receptor' for receptors activated during cancer progression.
- To review evidence supporting AIIt's role as an oncogenic plasminogen receptor and its potential as a cancer biomarker.
Main Methods:
- Review of existing research on cell surface plasminogen receptors, focusing on S100A10 and the AIIt complex.
- Discussion of molecular mechanisms involving AIIt in regulating plasmin formation and degradation.
- Analysis of studies linking AIIt activation to oncogenes (SRC, RAS, HIF1α, PML-RAR) and epigenetic modifications (DNA methylation) during epithelial-mesenchymal transition (EMT).
Main Results:
- AIIt is identified as a key regulator of both plasmin formation and destruction, functioning as the primary cellular plasminogen receptor.
- AIIt is established as an oncogenic plasminogen receptor, activated during EMT and by oncogenic signaling pathways.
- Animal models provide evidence for S100A10's involvement in tumor progression and oncogenesis.
Conclusions:
- The ANXA2/S100A10 (AIIt) complex is a critical regulator of plasmin generation and a significant factor in cancer progression.
- S100A10, as part of AIIt, functions as an oncogenic plasminogen receptor.
- S100A10 holds promise as a potential biomarker for cancer diagnosis and prognosis.
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