AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis
TRAF6-BECN1 signaling axis is critical for autophagy induction and functionally implicated in cancer progression. Here, we report that AMP-activated protein kinase alpha 1 (<i>AMPKα1</i>, <i>PRKAA1</i>) is positively involved in autophagy induction and cancer progression by r...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/11/3289 |
| _version_ | 1797548652200198144 |
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| author | Mi-Jeong Kim Yoon Min Juhee Son Ji Young Kim Ji Su Lee Duk-Hwan Kim Ki-Young Lee |
| author_facet | Mi-Jeong Kim Yoon Min Juhee Son Ji Young Kim Ji Su Lee Duk-Hwan Kim Ki-Young Lee |
| author_sort | Mi-Jeong Kim |
| collection | DOAJ |
| description | TRAF6-BECN1 signaling axis is critical for autophagy induction and functionally implicated in cancer progression. Here, we report that AMP-activated protein kinase alpha 1 (<i>AMPKα1</i>, <i>PRKAA1</i>) is positively involved in autophagy induction and cancer progression by regulating TRAF6-BECN1 signaling axis. Mechanistically, AMPKα1 interacted with TRAF6 and BECN1. It also enhanced ubiquitination of BECN1 and autophagy induction. <i>AMPKα1</i>-knockout (<i>AMPKα1</i>KO) HEK293T or <i>AMPKα1</i>-knockdown (<i>AMPKα1</i>KD) THP-1 cells showed impaired autophagy induced by serum starvation or TLR4 (Toll-like receptor 4) stimulation. Additionally, <i>AMPKα1</i>KD THP-1 cells showed decreases of autophagy-related and autophagosome-related genes induced by TLR4. <i>AMPKα1</i>KO A549 cells exhibited attenuation of cancer migration and invasion induced by TLR4. Moreover, primary non-small cell lung cancers (NSCLCs, <i>n</i> = 6) with low AMPKαl levels showed markedly decreased expression of genes related to autophagy, cell migration and adhesion/metastasis, inflammation, and TLRs whereas these genes were significantly upregulated in NSCLCs (<i>n</i> = 5) with high AMPKαl levels. Consistently, attenuation of cancer migration and invasion could be observed in <i>AMPKα1</i>KO MDA-MB-231 and <i>AMPKα1</i>KO MCF-7 human breast cancer cells. These results suggest that AMPKα1 plays a pivotal role in cancer progression by regulating the TRAF6-BECN1 signaling axis for autophagy induction. |
| first_indexed | 2024-03-10T15:02:40Z |
| format | Article |
| id | doaj.art-007702a9e06e4b1ca10a191f6d6bcd1d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:02:40Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-007702a9e06e4b1ca10a191f6d6bcd1d2023-11-20T20:01:20ZengMDPI AGCancers2072-66942020-11-011211328910.3390/cancers12113289AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling AxisMi-Jeong Kim0Yoon Min1Juhee Son2Ji Young Kim3Ji Su Lee4Duk-Hwan Kim5Ki-Young Lee6Department of Immunology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, KoreaDepartment of Immunology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, KoreaDepartment of Immunology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, KoreaDepartment of Immunology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, KoreaDepartment of Immunology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, KoreaDepartment of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, KoreaDepartment of Immunology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, KoreaTRAF6-BECN1 signaling axis is critical for autophagy induction and functionally implicated in cancer progression. Here, we report that AMP-activated protein kinase alpha 1 (<i>AMPKα1</i>, <i>PRKAA1</i>) is positively involved in autophagy induction and cancer progression by regulating TRAF6-BECN1 signaling axis. Mechanistically, AMPKα1 interacted with TRAF6 and BECN1. It also enhanced ubiquitination of BECN1 and autophagy induction. <i>AMPKα1</i>-knockout (<i>AMPKα1</i>KO) HEK293T or <i>AMPKα1</i>-knockdown (<i>AMPKα1</i>KD) THP-1 cells showed impaired autophagy induced by serum starvation or TLR4 (Toll-like receptor 4) stimulation. Additionally, <i>AMPKα1</i>KD THP-1 cells showed decreases of autophagy-related and autophagosome-related genes induced by TLR4. <i>AMPKα1</i>KO A549 cells exhibited attenuation of cancer migration and invasion induced by TLR4. Moreover, primary non-small cell lung cancers (NSCLCs, <i>n</i> = 6) with low AMPKαl levels showed markedly decreased expression of genes related to autophagy, cell migration and adhesion/metastasis, inflammation, and TLRs whereas these genes were significantly upregulated in NSCLCs (<i>n</i> = 5) with high AMPKαl levels. Consistently, attenuation of cancer migration and invasion could be observed in <i>AMPKα1</i>KO MDA-MB-231 and <i>AMPKα1</i>KO MCF-7 human breast cancer cells. These results suggest that AMPKα1 plays a pivotal role in cancer progression by regulating the TRAF6-BECN1 signaling axis for autophagy induction.https://www.mdpi.com/2072-6694/12/11/3289AMPKαltoll like receptor 4TRAF6-BECN1 signaling axisautophagycancer |
| spellingShingle | Mi-Jeong Kim Yoon Min Juhee Son Ji Young Kim Ji Su Lee Duk-Hwan Kim Ki-Young Lee AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis Cancers AMPKαl toll like receptor 4 TRAF6-BECN1 signaling axis autophagy cancer |
| title | AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis |
| title_full | AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis |
| title_fullStr | AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis |
| title_full_unstemmed | AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis |
| title_short | AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis |
| title_sort | ampkα1 regulates lung and breast cancer progression by regulating tlr4 mediated traf6 becn1 signaling axis |
| topic | AMPKαl toll like receptor 4 TRAF6-BECN1 signaling axis autophagy cancer |
| url | https://www.mdpi.com/2072-6694/12/11/3289 |
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