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Updated: Jun 16, 2025

Monitoring Breast Cancer Growth and Metastatic Colony Formation in Mice using Bioluminescence
Published on: November 5, 2021
Small protein ERSP encoded by LINC02870 promotes triple negative breast cancer progression via IRE1α/XBP1s activation
Xiaolu Wang1,2, Qianqian Wang1, Hong Wang1
1School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 510006, China.
Abstract:
Clinical treatment options for triple-negative breast cancer (TNBC) are currently limited to chemotherapy because of a lack of effective therapeutic targets. Recent evidence suggests that long noncoding RNAs (lncRNAs) encode bioactive peptides or proteins, thereby playing noncanonical yet significant roles in regulating cellular processes. However, the potential of lncRNA-translated products in cancer progression remains largely unknown. In this study, we identified a previously undocumented small protein encoded by the lncRNA LINC02870. This protein is localized at the endoplasmic reticulum (ER) and participates in ER stress, thus, we named it the endoplasmic reticulum stress protein (ERSP). ERSP was highly expressed in TNBC tissues, and elevated LINC02870 content was correlated with poor prognosis in TNBC patients. Loss of ERSP inhibited TNBC growth and metastasis both in vitro and in vivo. The pro-oncogenic effects of ERSP could be attributed to its selective activation of the IRE1α/XBP1s branch. ERSP enhances the unfolded protein response (UPR) by interacting with XBP1s, facilitating the nuclear accumulation of XBP1s, thereby promoting the expression of ER stress-related genes. These findings highlight the regulatory role of the lncRNA-encoded protein ERSP in ER stress and suggest that it is a potential therapeutic target for TNBC.
Insights
Researchers discovered a new protein, ERSP, encoded by LINC01870, that drives triple-negative breast cancer (TNBC) progression by activating ER stress. Targeting ERSP may offer new therapeutic strategies for TNBC.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies, relying primarily on chemotherapy.
- Long noncoding RNAs (lncRNAs) have emerging roles beyond non-coding functions, including encoding small proteins.
- The role of lncRNA-encoded proteins in cancer progression is largely unexplored.
Purpose of the Study:
- To identify and characterize novel lncRNA-encoded proteins involved in TNBC.
- To investigate the function of a newly identified protein, ERSP, in TNBC pathogenesis.
- To explore ERSP as a potential therapeutic target for TNBC.
Main Methods:
- Identification and characterization of a novel small protein (ERSP) encoded by LINC01870.
- Analysis of ERSP expression in TNBC tissues and correlation with patient prognosis.
- In vitro and in vivo studies to assess the impact of ERSP loss on TNBC growth and metastasis.
- Investigation of ERSP's mechanism of action involving the endoplasmic reticulum (ER) stress pathway, specifically the IRE1α/XBP1s branch.
Main Results:
- A novel small protein, ERSP, encoded by LINC01870, was identified and localized to the ER.
- ERSP expression was significantly elevated in TNBC tissues and correlated with poor patient prognosis.
- Loss of ERSP function suppressed TNBC cell growth and metastasis in vitro and in vivo.
- ERSP was found to activate the IRE1α/XBP1s pathway, enhancing the unfolded protein response (UPR) and promoting ER stress-related gene expression.
Conclusions:
- The lncRNA-encoded protein ERSP plays a significant pro-oncogenic role in TNBC by modulating ER stress.
- ERSP's activation of the IRE1α/XBP1s pathway is crucial for its oncogenic functions.
- ERSP represents a promising novel therapeutic target for triple-negative breast cancer.
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