PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells
Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer. The aberrant regulation of Paired box 6 (PAX6) expression has been proposed to play an important oncogenic role in several cancer types. Nevertheless, there is limited knowledge regarding its function in SCLC. Here, we find th...
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Elsevier
2025-01-01
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| author | Xiao-Fang Guo Ling-Ling Wang Fei-Meng Zheng He-Ping Li |
| author_facet | Xiao-Fang Guo Ling-Ling Wang Fei-Meng Zheng He-Ping Li |
| author_sort | Xiao-Fang Guo |
| collection | DOAJ |
| description | Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer. The aberrant regulation of Paired box 6 (PAX6) expression has been proposed to play an important oncogenic role in several cancer types. Nevertheless, there is limited knowledge regarding its function in SCLC. Here, we find that PAX6 overexpression promotes SCLC cell proliferation and cell cycle progression, while downregulation of PAX6 expression suppresses SCLC cell proliferation and cell cycle progression. Moreover, PAX6 enhances the enrichment of the ALDEFLUOR+ and CD133+ population and promotes sphere formation in SCLC cells. Additionally, upregulation or downregulation of PAX6 expression does not induce apoptosis in SCLC cells. Upregulation of PAX6 expression alleviates cisplatin or etoposide-induced apoptosis in SCLC cells, while downregulation of PAX6 expression aggravates cisplatin or etoposide-induced apoptosis in SCLC cells. Furthermore, PAX6 promotes the expression of stem cell factor Nanog. Interestingly, the downregulation of Nanog expression abolishes PAX6 promoted cell proliferation and cell cycle progression. Moreover, the inhibition of Nanog expression results in the inability of PAX6 to promote the increase of the ALDEFLUOR+ population, as well as the inability to mitigate apoptosis produced by cisplatin or etoposide in SCLC cells. Mechanically, PAX6 suppresses the activation of the NOTCH pathway to enhance Nanog expression. NOTCH pathway activation abolishes PAX6 promoted cell proliferation, cell cycle progression, ALDEFLUOR+ population enrichment, and apoptosis protection effect in SCLC cells. Our data indicates that PAX6 could be a critical factor for controlling cell proliferation, cell cycle progression, cancer stem cell properties, and apoptosis in SCLC. |
| format | Article |
| id | doaj-art-1c29ef9616164ceab549a37f28ff4a63 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-1c29ef9616164ceab549a37f28ff4a632025-02-02T05:28:13ZengElsevierHeliyon2405-84402025-01-01112e41795PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cellsXiao-Fang Guo0Ling-Ling Wang1Fei-Meng Zheng2He-Ping Li3Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Breast Surgery, Heyuan Women and Children's Hospital and Health Institute, Heyuan, Guangdong, ChinaDepartment of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Corresponding author. Department of Medical Oncology of The Eastern Hospital, The First Affiliated Hospital, Sun Yat-sen University, No.58, Zhong Shan Er Lu, Guangzhou, 510080, China.Department of Medical Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Corresponding author. Department of Medical Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang West Road, Guangzhou, 510080, China.Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer. The aberrant regulation of Paired box 6 (PAX6) expression has been proposed to play an important oncogenic role in several cancer types. Nevertheless, there is limited knowledge regarding its function in SCLC. Here, we find that PAX6 overexpression promotes SCLC cell proliferation and cell cycle progression, while downregulation of PAX6 expression suppresses SCLC cell proliferation and cell cycle progression. Moreover, PAX6 enhances the enrichment of the ALDEFLUOR+ and CD133+ population and promotes sphere formation in SCLC cells. Additionally, upregulation or downregulation of PAX6 expression does not induce apoptosis in SCLC cells. Upregulation of PAX6 expression alleviates cisplatin or etoposide-induced apoptosis in SCLC cells, while downregulation of PAX6 expression aggravates cisplatin or etoposide-induced apoptosis in SCLC cells. Furthermore, PAX6 promotes the expression of stem cell factor Nanog. Interestingly, the downregulation of Nanog expression abolishes PAX6 promoted cell proliferation and cell cycle progression. Moreover, the inhibition of Nanog expression results in the inability of PAX6 to promote the increase of the ALDEFLUOR+ population, as well as the inability to mitigate apoptosis produced by cisplatin or etoposide in SCLC cells. Mechanically, PAX6 suppresses the activation of the NOTCH pathway to enhance Nanog expression. NOTCH pathway activation abolishes PAX6 promoted cell proliferation, cell cycle progression, ALDEFLUOR+ population enrichment, and apoptosis protection effect in SCLC cells. Our data indicates that PAX6 could be a critical factor for controlling cell proliferation, cell cycle progression, cancer stem cell properties, and apoptosis in SCLC.http://www.sciencedirect.com/science/article/pii/S2405844025001756PAX6Small cell lung cancerCancer stem cellDrug resistanceNOTCHNanog |
| spellingShingle | Xiao-Fang Guo Ling-Ling Wang Fei-Meng Zheng He-Ping Li PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells Heliyon PAX6 Small cell lung cancer Cancer stem cell Drug resistance NOTCH Nanog |
| title | PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells |
| title_full | PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells |
| title_fullStr | PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells |
| title_full_unstemmed | PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells |
| title_short | PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells |
| title_sort | pax6 enhances nanog expression by inhibiting notch signaling to promote malignant properties in small cell lung cancer cells |
| topic | PAX6 Small cell lung cancer Cancer stem cell Drug resistance NOTCH Nanog |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025001756 |
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