C/EBPβ Regulates HIF-1α-Driven Invasion of Non-Small-Cell Lung Cancer Cells
Metastatic cancer accounts for most cancer-related deaths, and identifying specific molecular targets that contribute to metastatic progression is crucial for the development of effective treatments. Hypoxia, a feature of solid tumors, plays a role in cancer progression by inducing resistance to the...
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MDPI AG
2024-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/1/36 |
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| author | Seung Hee Seo Ji Hae Lee Eun Kyung Choi Seung Bae Rho Kyungsil Yoon |
| author_facet | Seung Hee Seo Ji Hae Lee Eun Kyung Choi Seung Bae Rho Kyungsil Yoon |
| author_sort | Seung Hee Seo |
| collection | DOAJ |
| description | Metastatic cancer accounts for most cancer-related deaths, and identifying specific molecular targets that contribute to metastatic progression is crucial for the development of effective treatments. Hypoxia, a feature of solid tumors, plays a role in cancer progression by inducing resistance to therapy and accelerating metastasis. Here, we report that CCAAT/enhancer-binding protein beta (C/EBPβ) transcriptionally regulates <i>hypoxia-inducible factor 1 subunit alpha</i> (<i>HIF1A</i>) and thus promotes migration and invasion of non-small-cell lung cancer (NSCLC) cells under hypoxic conditions. Our results show that knockdown or forced expression of C/EBPβ was correlated with HIF-1α expression and that C/EBPβ directly bound to the promoter region of <i>HIF1A</i>. Silencing <i>HIF1A</i> inhibited the enhanced migration and invasion induced by C/EBPβ overexpression in NSCLC cells under hypoxia. Expression of the HIF-1α target gene, <i>SLC2A1</i>, was also altered in a C/EBPβ-dependent manner, and knockdown of <i>SLC2A1</i> reduced migration and invasion enhanced by C/EBPβ overexpression. These results indicate that C/EBPβ is a critical regulator for the invasion of NSCLC cells in the hypoxic tumor microenvironment. Collectively, the C/EBPβ-HIF-1α-GLUT1 axis represents a potential therapeutic target for preventing metastatic progression of NSCLC and improving patient outcomes. |
| format | Article |
| id | doaj-art-731975892c074012b6652427ffeac2b2 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-731975892c074012b6652427ffeac2b22025-01-24T13:24:56ZengMDPI AGBiomolecules2218-273X2024-12-011513610.3390/biom15010036C/EBPβ Regulates HIF-1α-Driven Invasion of Non-Small-Cell Lung Cancer CellsSeung Hee Seo0Ji Hae Lee1Eun Kyung Choi2Seung Bae Rho3Kyungsil Yoon4Cancer Metastasis Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaCancer Metastasis Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaCancer Metastasis Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaCancer Metastasis Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaCancer Metastasis Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaMetastatic cancer accounts for most cancer-related deaths, and identifying specific molecular targets that contribute to metastatic progression is crucial for the development of effective treatments. Hypoxia, a feature of solid tumors, plays a role in cancer progression by inducing resistance to therapy and accelerating metastasis. Here, we report that CCAAT/enhancer-binding protein beta (C/EBPβ) transcriptionally regulates <i>hypoxia-inducible factor 1 subunit alpha</i> (<i>HIF1A</i>) and thus promotes migration and invasion of non-small-cell lung cancer (NSCLC) cells under hypoxic conditions. Our results show that knockdown or forced expression of C/EBPβ was correlated with HIF-1α expression and that C/EBPβ directly bound to the promoter region of <i>HIF1A</i>. Silencing <i>HIF1A</i> inhibited the enhanced migration and invasion induced by C/EBPβ overexpression in NSCLC cells under hypoxia. Expression of the HIF-1α target gene, <i>SLC2A1</i>, was also altered in a C/EBPβ-dependent manner, and knockdown of <i>SLC2A1</i> reduced migration and invasion enhanced by C/EBPβ overexpression. These results indicate that C/EBPβ is a critical regulator for the invasion of NSCLC cells in the hypoxic tumor microenvironment. Collectively, the C/EBPβ-HIF-1α-GLUT1 axis represents a potential therapeutic target for preventing metastatic progression of NSCLC and improving patient outcomes.https://www.mdpi.com/2218-273X/15/1/36C/EBPβhypoxiaHIF-1αmetastasisnon-small-cell lung cancer |
| spellingShingle | Seung Hee Seo Ji Hae Lee Eun Kyung Choi Seung Bae Rho Kyungsil Yoon C/EBPβ Regulates HIF-1α-Driven Invasion of Non-Small-Cell Lung Cancer Cells Biomolecules C/EBPβ hypoxia HIF-1α metastasis non-small-cell lung cancer |
| title | C/EBPβ Regulates HIF-1α-Driven Invasion of Non-Small-Cell Lung Cancer Cells |
| title_full | C/EBPβ Regulates HIF-1α-Driven Invasion of Non-Small-Cell Lung Cancer Cells |
| title_fullStr | C/EBPβ Regulates HIF-1α-Driven Invasion of Non-Small-Cell Lung Cancer Cells |
| title_full_unstemmed | C/EBPβ Regulates HIF-1α-Driven Invasion of Non-Small-Cell Lung Cancer Cells |
| title_short | C/EBPβ Regulates HIF-1α-Driven Invasion of Non-Small-Cell Lung Cancer Cells |
| title_sort | c ebpβ regulates hif 1α driven invasion of non small cell lung cancer cells |
| topic | C/EBPβ hypoxia HIF-1α metastasis non-small-cell lung cancer |
| url | https://www.mdpi.com/2218-273X/15/1/36 |
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