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Updated: Jan 21, 2026
09:29
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
18.8K
Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating
Anbarasu Kannan1, Julie V Philley2, Kate L Hertweck3,4
1Departments of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
Scientific Reports
|August 14, 2019
Summary
Triple negative breast cancer (TNBC) promotes metastasis via SPANXB1. Targeting SPANXB1 in extracellular vesicles offers a novel therapeutic strategy and prognostic biomarker for improving TNBC survival.
Area of Science:
- Oncology
- Cancer Metastasis Research
- Biomarker Discovery
Background:
- Triple negative breast cancer (TNBC) is characterized by poor prognosis, rapid metastasis, and a lack of effective targeted therapies and reliable prognostic markers.
- Cancer-testis antigens, such as SPANXB1, are increasingly recognized for their roles in tumor progression and metastasis.
- Small extracellular vesicles (sEVs) are emerging as important mediators of intercellular communication in cancer and potential sources of biomarkers.
Purpose of the Study:
- To investigate the metastasis-promoting role of the cancer-testis antigen SPANXB1 in TNBC.
- To evaluate the utility of SPANXB1 as a therapeutic target and prognostic biomarker in TNBC.
- To determine the expression pattern of SPANXB1 in primary tumors, metastatic tissues, and circulating sEVs.
Main Methods:
- Expression analysis of SPANXB1 in matched primary TNBC, lymph node metastases, and circulating sEVs.
- cDNA microarray analysis to identify potential target genes of the metastasis suppressor SH3GL2 in TNBC cells.
- Functional assays including gene silencing and overexpression to assess the impact of SPANXB1 on TNBC cell migration, invasion, and ROS production.
- Analysis of downstream molecular targets affected by SPANXB1 modulation.
- In vivo metastasis assays in mouse models.
- Detection and characterization of SPANXB1 in circulating sEVs.
Main Results:
- Silencing SPANXB1 reduced TNBC cell migration, invasion, and reactive oxygen species (ROS) production, while augmenting SH3GL2 expression and decreasing RAC-1, FAK, A-Actinin, and Vinculin.
- Overexpression of SPANXB1 in breast cancer cells led to enhanced pulmonary metastasis, correlating with an increased SPANXB1:SH3GL2 ratio.
- Altered SPANXB1 expression was detected in circulating sEVs, with exclusive expression traceable in sEVs associated with TNBC progression.
- SH3GL2 overexpression in TNBC cells led to decreased SPANXB1 mRNA and protein levels.
Conclusions:
- SPANXB1 plays a significant role in promoting metastasis in triple negative breast cancer.
- SPANXB1 represents a novel and promising therapeutic target for inhibiting TNBC metastasis due to its unique expression profile.
- SPANXB1, detectable in circulating extracellular vesicles, may serve as a valuable EV-based prognostic marker to improve TNBC patient survival and guide targeted therapies.
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