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Published on: January 18, 2017
AF1q inhibited T cell attachment to breast cancer cell by attenuating Intracellular Adhesion Molecule-1 expression
Jino Park1,2, Jae Yeon Hwang3, Alexandra Thore1,2
1James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Aim:
To investigate whether AF1q, overexpressed in metastatic cells compared with the primary tumor cells, plays a pivotal role in breast cancer metastasis.
Methods:
To investigate whether AF1q has a responsibility in the acquisition of a metastatic phenotype, we performed RNA-sequencing (RNA-Seq) to identify the gene signature and applied the Metacore direct interactions network building algorithm with the top 40 amplicons of RNA-Seq.
Results:
Most genes were directly linked with intercellular adhesion molecule-1 (ICAM-1). Likewise, we identified that ICAM-1 expression is attenuated in metastatic cells compared to primary tumor cells. Moreover, overexpression of AF1q attenuated ICAM-1 expression, whereas suppression of AF1q elicited the opposite effect. AF1q had an effect on ICAM-1 promoter region and regulated its transcription. Decreased ICAM-1 expression affected the attachment of T cells to a breast cancer cell monolayer. We confirmed the finding by performing the analysis on Burkitt's lymphoma.
Conclusion:
Attenuation of ICAM-1 by AF1q on tumor cells disadvantages host anti-tumor defenses through the trafficking of lymphocytes, which affects tumor progression and metastasis.
Insights
AF1q overexpression in metastatic breast cancer cells reduces intercellular adhesion molecule-1 (ICAM-1) expression, hindering anti-tumor immune responses and promoting metastasis. This finding impacts understanding of tumor progression and immune evasion.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- AF1q is overexpressed in metastatic breast cancer cells compared to primary tumor cells.
- The role of AF1q in breast cancer metastasis is not fully understood.
Purpose of the Study:
- To investigate the role of AF1q in breast cancer metastasis.
- To identify the molecular mechanisms by which AF1q influences metastasis.
Main Methods:
- RNA-sequencing (RNA-Seq) was used to identify the gene signature associated with AF1q.
- Metacore direct interactions network building algorithm was applied to analyze RNA-Seq data.
- ICAM-1 expression and its regulation by AF1q were investigated.
Main Results:
- AF1q overexpression attenuates ICAM-1 expression in metastatic cells.
- AF1q directly regulates ICAM-1 transcription.
- Decreased ICAM-1 expression impairs T cell attachment to cancer cells.
- Findings were validated in Burkitt's lymphoma.
Conclusions:
- AF1q-mediated attenuation of ICAM-1 on tumor cells compromises host anti-tumor immunity.
- This mechanism facilitates tumor progression and metastasis by affecting lymphocyte trafficking.
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