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HMGA1, Moonlighting Protein Function, and Cellular Real Estate: Location, Location, Location!
Mireia Pujals1, Linda Resar2,3,4, Josep Villanueva1,5
1Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
Biomolecules
|September 28, 2021
Summary
High Mobility Group A1 (HMGA1) acts as a nuclear regulator and a secreted factor driving cancer progression. Targeting extracellular HMGA1 offers novel therapeutic opportunities for cancers overexpressing this protein.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- High Mobility Group A1 (HMGA1) is a chromatin remodeling protein often upregulated in cancers, correlating with poor clinical outcomes.
- HMGA1 was traditionally considered a nuclear protein regulating gene expression and signaling pathways in cancer and stem cells.
Purpose of the Study:
- To review the dual role of HMGA1 as both a nuclear regulator and a secreted factor in tumor progression.
- To highlight the implications of extracellular HMGA1 in invasive triple-negative breast cancer (TNBC) and its potential as a therapeutic target.
Main Methods:
- Review of existing literature on HMGA1's function in cancer.
- Analysis of studies investigating HMGA1 secretion in TNBC cell lines and primary tumors.
Main Results:
- HMGA1 functions as a "moonlighting protein" with distinct roles depending on its cellular localization (nuclear vs. extracellular).
- An extracellular HMGA1-RAGE autocrine loop promotes tumor invasion and metastasis in TNBC.
- HMGA1 secretion in primary TNBC tumors is associated with distant metastasis.
Conclusions:
- Extracellular HMGA1 plays a significant role in driving tumor progression, invasion, and metastasis.
- Targeting secreted HMGA1 presents a promising therapeutic strategy for various human cancers.
- Further research is warranted to confirm the role of extracellular HMGA1 in diverse cancer contexts and explore nuclear-secreted crosstalk.
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