Autophagy inhibits cancer stemness in triple‐negative breast cancer via miR‐181a‐mediated regulation of ATG5 and/or ATG2B
Autophagy has a dual role in the maintenance of cancer stem cells (CSCs), but the precise relationship between autophagy and cancer stemness requires further investigation. In this study, it was found that luminal and triple‐negative breast cancers require distinct therapeutic approaches because of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-05-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13180 |
| _version_ | 1818029266152980480 |
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| author | Jee Won Park Yesol Kim Soo‐been Lee Chae Won Oh Eun Ji Lee Je Yeong Ko Jong Hoon Park |
| author_facet | Jee Won Park Yesol Kim Soo‐been Lee Chae Won Oh Eun Ji Lee Je Yeong Ko Jong Hoon Park |
| author_sort | Jee Won Park |
| collection | DOAJ |
| description | Autophagy has a dual role in the maintenance of cancer stem cells (CSCs), but the precise relationship between autophagy and cancer stemness requires further investigation. In this study, it was found that luminal and triple‐negative breast cancers require distinct therapeutic approaches because of their different amounts of autophagy flux. We identified that autophagy flux was inhibited in triple‐negative breast cancer (TNBC) CSCs. Moreover, miRNA‐181a (miR‐181a) expression is upregulated in both TNBC CSCs and patient tissues. Autophagy‐related 5 (ATG5) and autophagy‐related 2B (ATG2B) participate in the early formation of autophagosomes and were revealed as targets of miR‐181a. Inhibition of miR‐181a expression led to attenuation of TNBC stemness and an increase in autophagy flux. Furthermore, treatment with curcumin led to attenuation of cancer stemness in TNBC CSCs; the expression of ATG5 and ATG2B was enhanced and there was an increase of autophagy flux. These results indicated that ATG5 and ATG2B are involved in the suppression of cancer stemness in TNBC. In summary, autophagy inhibits cancer stemness through the miR‐181a‐regulated mechanism in TNBC. Promoting tumor‐suppressive autophagy using curcumin may be a potential method for the treatment of TNBC. |
| first_indexed | 2024-12-10T05:16:57Z |
| format | Article |
| id | doaj.art-59993a42eabd4b96ab9095e5b24716dd |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-10T05:16:57Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-59993a42eabd4b96ab9095e5b24716dd2022-12-22T02:00:57ZengWileyMolecular Oncology1574-78911878-02612022-05-011691857187510.1002/1878-0261.13180Autophagy inhibits cancer stemness in triple‐negative breast cancer via miR‐181a‐mediated regulation of ATG5 and/or ATG2BJee Won Park0Yesol Kim1Soo‐been Lee2Chae Won Oh3Eun Ji Lee4Je Yeong Ko5Jong Hoon Park6Department of Biological Science Sookmyung Women’s University Seoul Republic of KoreaDepartment of Biological Science Sookmyung Women’s University Seoul Republic of KoreaDepartment of Biological Science Sookmyung Women’s University Seoul Republic of KoreaDepartment of Biological Science Sookmyung Women’s University Seoul Republic of KoreaDepartment of Biological Science Sookmyung Women’s University Seoul Republic of KoreaDepartment of Biological Science Sookmyung Women’s University Seoul Republic of KoreaDepartment of Biological Science Sookmyung Women’s University Seoul Republic of KoreaAutophagy has a dual role in the maintenance of cancer stem cells (CSCs), but the precise relationship between autophagy and cancer stemness requires further investigation. In this study, it was found that luminal and triple‐negative breast cancers require distinct therapeutic approaches because of their different amounts of autophagy flux. We identified that autophagy flux was inhibited in triple‐negative breast cancer (TNBC) CSCs. Moreover, miRNA‐181a (miR‐181a) expression is upregulated in both TNBC CSCs and patient tissues. Autophagy‐related 5 (ATG5) and autophagy‐related 2B (ATG2B) participate in the early formation of autophagosomes and were revealed as targets of miR‐181a. Inhibition of miR‐181a expression led to attenuation of TNBC stemness and an increase in autophagy flux. Furthermore, treatment with curcumin led to attenuation of cancer stemness in TNBC CSCs; the expression of ATG5 and ATG2B was enhanced and there was an increase of autophagy flux. These results indicated that ATG5 and ATG2B are involved in the suppression of cancer stemness in TNBC. In summary, autophagy inhibits cancer stemness through the miR‐181a‐regulated mechanism in TNBC. Promoting tumor‐suppressive autophagy using curcumin may be a potential method for the treatment of TNBC.https://doi.org/10.1002/1878-0261.13180ATG2BATG5autophagycancer stemnessmiR‐181atriple‐negative breast cancer |
| spellingShingle | Jee Won Park Yesol Kim Soo‐been Lee Chae Won Oh Eun Ji Lee Je Yeong Ko Jong Hoon Park Autophagy inhibits cancer stemness in triple‐negative breast cancer via miR‐181a‐mediated regulation of ATG5 and/or ATG2B Molecular Oncology ATG2B ATG5 autophagy cancer stemness miR‐181a triple‐negative breast cancer |
| title | Autophagy inhibits cancer stemness in triple‐negative breast cancer via miR‐181a‐mediated regulation of ATG5 and/or ATG2B |
| title_full | Autophagy inhibits cancer stemness in triple‐negative breast cancer via miR‐181a‐mediated regulation of ATG5 and/or ATG2B |
| title_fullStr | Autophagy inhibits cancer stemness in triple‐negative breast cancer via miR‐181a‐mediated regulation of ATG5 and/or ATG2B |
| title_full_unstemmed | Autophagy inhibits cancer stemness in triple‐negative breast cancer via miR‐181a‐mediated regulation of ATG5 and/or ATG2B |
| title_short | Autophagy inhibits cancer stemness in triple‐negative breast cancer via miR‐181a‐mediated regulation of ATG5 and/or ATG2B |
| title_sort | autophagy inhibits cancer stemness in triple negative breast cancer via mir 181a mediated regulation of atg5 and or atg2b |
| topic | ATG2B ATG5 autophagy cancer stemness miR‐181a triple‐negative breast cancer |
| url | https://doi.org/10.1002/1878-0261.13180 |
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