The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer
Abstract The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cance...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-05-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-021-00259-z |
| _version_ | 1827776795285389312 |
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| author | Zhenbo Tu Johannes Schmoellerl Odette Mariani Yurong Zheng Yi Hu Anne Vincent-Salomon Antoine E. Karnoub |
| author_facet | Zhenbo Tu Johannes Schmoellerl Odette Mariani Yurong Zheng Yi Hu Anne Vincent-Salomon Antoine E. Karnoub |
| author_sort | Zhenbo Tu |
| collection | DOAJ |
| description | Abstract The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades would better our understanding of TNBC biology and bring about therapeutics that eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of RNAs called long non-coding RNAs or lncRNAs and utilized a MSC-supported TNBC progression model to identify specific family members of functional relevance to TNBC pathogenesis. Indeed, although some have been described to play functional roles in TNBC, activities of lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulate robust expression of LINC01119 in TNBC cells, which in turn induces suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy. |
| first_indexed | 2024-03-11T14:09:41Z |
| format | Article |
| id | doaj.art-eb5b212410734bcb9411cb9cb050eda5 |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-11T14:09:41Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-eb5b212410734bcb9411cb9cb050eda52023-11-02T00:47:42ZengNature Portfolionpj Breast Cancer2374-46772021-05-017111310.1038/s41523-021-00259-zThe LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancerZhenbo Tu0Johannes Schmoellerl1Odette Mariani2Yurong Zheng3Yi Hu4Anne Vincent-Salomon5Antoine E. Karnoub6Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical SchoolInstitut CurieDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical SchoolInstitut CurieDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical SchoolAbstract The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades would better our understanding of TNBC biology and bring about therapeutics that eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of RNAs called long non-coding RNAs or lncRNAs and utilized a MSC-supported TNBC progression model to identify specific family members of functional relevance to TNBC pathogenesis. Indeed, although some have been described to play functional roles in TNBC, activities of lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulate robust expression of LINC01119 in TNBC cells, which in turn induces suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy.https://doi.org/10.1038/s41523-021-00259-z |
| spellingShingle | Zhenbo Tu Johannes Schmoellerl Odette Mariani Yurong Zheng Yi Hu Anne Vincent-Salomon Antoine E. Karnoub The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer npj Breast Cancer |
| title | The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer |
| title_full | The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer |
| title_fullStr | The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer |
| title_full_unstemmed | The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer |
| title_short | The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer |
| title_sort | linc01119 socs5 axis as a critical theranostic in triple negative breast cancer |
| url | https://doi.org/10.1038/s41523-021-00259-z |
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