Kruppel-like factor 4 inhibits non–small cell lung cancer cell growth and aggressiveness by stimulating transforming growth factor-β1-meidated ERK/JNK/NF-κB signaling pathways
Non–small cell lung cancer is one of the most common epithelial tumors that cause the most common cancer-related mortality due to invasive ability. Research has found that Kruppel-like factor 4, a zinc-finger transcription factor, plays a critical role in the tumor evolution and progression. However...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-06-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317705574 |
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| author | Renzhi Yu Lei Han Xin Ni Minghuan Wang Ping Xue Li Zhang Mei Yuan |
| author_facet | Renzhi Yu Lei Han Xin Ni Minghuan Wang Ping Xue Li Zhang Mei Yuan |
| author_sort | Renzhi Yu |
| collection | DOAJ |
| description | Non–small cell lung cancer is one of the most common epithelial tumors that cause the most common cancer-related mortality due to invasive ability. Research has found that Kruppel-like factor 4, a zinc-finger transcription factor, plays a critical role in the tumor evolution and progression. However, the molecular signal pathways mediated by Kruppel-like factor 4 in the progression of non–small cell lung cancer cells have not been well understood yet. In this study, we investigated the possible role and potential mechanism of Kruppel-like factor 4 in growth and aggressiveness of non–small cell lung cancer cells. Results showed that Kruppel-like factor 4 is downregulated in non–small cell lung cancer cells. Here, we found that Kruppel-like factor 4 knockdown promoted growth and aggressiveness of non–small cell lung cancer cells, as well as enhanced apoptotic resistance induced by tunicamycin. We also found that Kruppel-like factor 4 overexpression significantly suppressed growth and aggressiveness of non–small cell lung cancer cells. Apoptosis rate of non–small cell lung cancer cells induced by tunicamycin was promoted by Kruppel-like factor 4 overexpression. Kruppel-like factor 4 overexpression inhibited transforming growth factor-β1, extracellular signal–regulated protein kinase, C-jun N-terminal kinase, and nuclear factor-κB expression levels in non–small cell lung cancer cells. Mechanistically, Kruppel-like factor 4–mediated tumorigenesis involved suppression of a transforming growth factor-β1-meidated extracellular signal–regulated protein kinase/C-jun N-terminal kinase/nuclear factor-κB transcriptional program in non–small cell lung cancer cells. Our results revealed that Kruppel-like factor 4 overexpression non–small cell lung cancer cell reduces tumor growth in experimental mice. Overall, these data indicate the inhibitory role of Kruppel-like factor 4 in non–small cell lung cancer cells and elaborate a potential molecular signal pathway involving in growth and aggressiveness. Findings identify Kruppel-like factor 4 can be regarded as a possible new molecular agent for designing novel therapeutic protein drug for lung cancer treatment to control non–small cell lung cancer growth. |
| format | Article |
| id | doaj-art-e8fd79577d6346d8bb76fdd9a2dda182 |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-e8fd79577d6346d8bb76fdd9a2dda1822025-08-20T03:57:54ZengSAGE PublishingTumor Biology1423-03802017-06-013910.1177/1010428317705574Kruppel-like factor 4 inhibits non–small cell lung cancer cell growth and aggressiveness by stimulating transforming growth factor-β1-meidated ERK/JNK/NF-κB signaling pathwaysRenzhi Yu0Lei Han1Xin Ni2Minghuan Wang3Ping Xue4Li Zhang5Mei Yuan6Department of Respiratory Medicine, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, ChinaDepartment of Respiratory Medicine, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, ChinaDepartment of Respiratory Medicine, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, ChinaCommunity Health Service Center, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, ChinaDepartment of Respiratory Medicine, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, ChinaDepartment of Respiratory Medicine, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, ChinaDepartment of Respiratory Medicine, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, ChinaNon–small cell lung cancer is one of the most common epithelial tumors that cause the most common cancer-related mortality due to invasive ability. Research has found that Kruppel-like factor 4, a zinc-finger transcription factor, plays a critical role in the tumor evolution and progression. However, the molecular signal pathways mediated by Kruppel-like factor 4 in the progression of non–small cell lung cancer cells have not been well understood yet. In this study, we investigated the possible role and potential mechanism of Kruppel-like factor 4 in growth and aggressiveness of non–small cell lung cancer cells. Results showed that Kruppel-like factor 4 is downregulated in non–small cell lung cancer cells. Here, we found that Kruppel-like factor 4 knockdown promoted growth and aggressiveness of non–small cell lung cancer cells, as well as enhanced apoptotic resistance induced by tunicamycin. We also found that Kruppel-like factor 4 overexpression significantly suppressed growth and aggressiveness of non–small cell lung cancer cells. Apoptosis rate of non–small cell lung cancer cells induced by tunicamycin was promoted by Kruppel-like factor 4 overexpression. Kruppel-like factor 4 overexpression inhibited transforming growth factor-β1, extracellular signal–regulated protein kinase, C-jun N-terminal kinase, and nuclear factor-κB expression levels in non–small cell lung cancer cells. Mechanistically, Kruppel-like factor 4–mediated tumorigenesis involved suppression of a transforming growth factor-β1-meidated extracellular signal–regulated protein kinase/C-jun N-terminal kinase/nuclear factor-κB transcriptional program in non–small cell lung cancer cells. Our results revealed that Kruppel-like factor 4 overexpression non–small cell lung cancer cell reduces tumor growth in experimental mice. Overall, these data indicate the inhibitory role of Kruppel-like factor 4 in non–small cell lung cancer cells and elaborate a potential molecular signal pathway involving in growth and aggressiveness. Findings identify Kruppel-like factor 4 can be regarded as a possible new molecular agent for designing novel therapeutic protein drug for lung cancer treatment to control non–small cell lung cancer growth.https://doi.org/10.1177/1010428317705574 |
| spellingShingle | Renzhi Yu Lei Han Xin Ni Minghuan Wang Ping Xue Li Zhang Mei Yuan Kruppel-like factor 4 inhibits non–small cell lung cancer cell growth and aggressiveness by stimulating transforming growth factor-β1-meidated ERK/JNK/NF-κB signaling pathways Tumor Biology |
| title | Kruppel-like factor 4 inhibits non–small cell lung cancer cell growth and aggressiveness by stimulating transforming growth factor-β1-meidated ERK/JNK/NF-κB signaling pathways |
| title_full | Kruppel-like factor 4 inhibits non–small cell lung cancer cell growth and aggressiveness by stimulating transforming growth factor-β1-meidated ERK/JNK/NF-κB signaling pathways |
| title_fullStr | Kruppel-like factor 4 inhibits non–small cell lung cancer cell growth and aggressiveness by stimulating transforming growth factor-β1-meidated ERK/JNK/NF-κB signaling pathways |
| title_full_unstemmed | Kruppel-like factor 4 inhibits non–small cell lung cancer cell growth and aggressiveness by stimulating transforming growth factor-β1-meidated ERK/JNK/NF-κB signaling pathways |
| title_short | Kruppel-like factor 4 inhibits non–small cell lung cancer cell growth and aggressiveness by stimulating transforming growth factor-β1-meidated ERK/JNK/NF-κB signaling pathways |
| title_sort | kruppel like factor 4 inhibits non small cell lung cancer cell growth and aggressiveness by stimulating transforming growth factor β1 meidated erk jnk nf κb signaling pathways |
| url | https://doi.org/10.1177/1010428317705574 |
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