A Cell-Based Systematic Review on the Role of Annexin A1 in Triple-Negative Breast Cancers
Lishantini Pearanpan1, Fariza Juliana Nordin1,2, Ee Ling Siew3,4,5
1Biomedical Science Program, Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd Aziz, Kuala Lumpur 50300, Malaysia.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy. Increasing evidence highlights the exploitability of Annexin A1 (AnxA1), a calcium dependent protein, as a precision medicine for TNBC. To systematically summarize the role of AnxA1 and its associated mechanisms in TNBC, we performed data mining using three main databases: PubMed, Scopus, and Ovid/Medline. The papers retrieved were based on two different sets of key words such as "Annexin A1" or "Lipocortin 1" and "Breast cancer" or "TNBC". A total of 388 articles were identified, with 210 chosen for comprehensive screening and 13 papers that met inclusion criteria were included. Current evidence from cell culture studies showed that AnxA1 expression is correlated with NF-κB, which promotes migration by activating ERK phosphorylation. AnxaA1 also activates TGF-β signaling which upregulates MMP-9 and miR196a expression to enhance epithelial-mesenchymal transition and migratory capacity of TNBC cells. AnxA1 can steer the macrophage polarization toward the M2 phenotype to create a pro-tumor immune environment. Existing research suggests a potential role of AnxA1 in the metastasis and immune landscape of TNBC tumors. Preclinical and clinical experiments are warranted to investigate the feasibility and effectiveness of targeting AnxA1 in TNBC.
Insights
Annexin A1 (AnxA1) plays a key role in triple-negative breast cancer (TNBC) progression by promoting cell migration and immune evasion. Targeting AnxA1 may offer a novel precision medicine strategy for TNBC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.
- Annexin A1 (AnxA1) is implicated in TNBC pathogenesis.
- AnxA1's role and mechanisms in TNBC require systematic summarization.
Purpose of the Study:
- To systematically review the literature on Annexin A1's role and mechanisms in triple-negative breast cancer.
- To identify AnxA1-associated pathways involved in TNBC progression.
Main Methods:
- Systematic literature review and data mining.
- Databases searched: PubMed, Scopus, Ovid/Medline.
- Inclusion criteria applied to 210 screened articles, with 13 selected for analysis.
Main Results:
- AnxA1 expression correlates with NF-κB and ERK phosphorylation, enhancing TNBC cell migration.
- AnxA1 activates TGF-β signaling, upregulating MMP-9 and miR196a, promoting epithelial-mesenchymal transition.
- AnxA1 influences macrophage polarization to an M2 phenotype, fostering a pro-tumor immune microenvironment.
Conclusions:
- AnxA1 is implicated in TNBC metastasis and immune modulation.
- Targeting AnxA1 presents a potential precision medicine approach for TNBC.
- Further preclinical and clinical studies are necessary to validate AnxA1 as a therapeutic target.
