Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9
Abstract Pancreatic cancer is a lethal disease with an insidious onset, and little is known about its early molecular events. Here, we found that the sterol regulatory element-binding protein 1 (SREBP1) expression is gradually upregulated during the initiation of pancreatic cancer. Through in vitro...
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2025-01-01
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| Series: | Biology Direct |
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| Online Access: | https://doi.org/10.1186/s13062-025-00595-1 |
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| author | Cancan Zhou Zhengyuan Feng Weikun Qian Zeen Zhu Ruiqi Cao Qiqi Wang Wunai Zhang Rujuan Liu Shuai Wu Jie Hao Zheng Wang Qingyong Ma Zheng Wu Xuqi Li |
| author_facet | Cancan Zhou Zhengyuan Feng Weikun Qian Zeen Zhu Ruiqi Cao Qiqi Wang Wunai Zhang Rujuan Liu Shuai Wu Jie Hao Zheng Wang Qingyong Ma Zheng Wu Xuqi Li |
| author_sort | Cancan Zhou |
| collection | DOAJ |
| description | Abstract Pancreatic cancer is a lethal disease with an insidious onset, and little is known about its early molecular events. Here, we found that the sterol regulatory element-binding protein 1 (SREBP1) expression is gradually upregulated during the initiation of pancreatic cancer. Through in vitro 3D culture of pancreatic acinar cells and experiments in LSL-Kras G12D/+ ;Pdx1-Cre (KC) mice, we found that pharmacological inhibition of SREBP1 suppressed pancreatic tumorigenesis. In vitro, either knockdown or pharmacological inhibition of SREBP1 suppressed tumor proliferation but SREBP1 overexpression promoted tumor proliferation. In LSL-Kras G12D/+ ;Trp53 fl/+ ;Pdx1-Cre (KPC) mice, we confirmed the tumor-promoting role of SREBP1 in pancreatic cancer progression. Mechanistically, we revealed SOX9 as a downstream target of SREPB1. SREBP1 inhibition decreased SOX9 expression in both acinar cells and pancreatic cancer cells. Indeed, we identified SREBP1 binding sites in the SOX9 promoter region and reported that SOX9 is transcriptionally regulated by SREBP1. Taken together, our findings demonstrate that SREBP1/SOX9 inhibition suppresses pancreatic cancer initiation and growth, suggesting that SREBP1 could serve as a potential target for cancer screening and treatment. |
| format | Article |
| id | doaj-art-b3904bff276347b89d8b5fd63e68400d |
| institution | Kabale University |
| issn | 1745-6150 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj-art-b3904bff276347b89d8b5fd63e68400d2025-01-19T12:13:22ZengBMCBiology Direct1745-61502025-01-0120111410.1186/s13062-025-00595-1Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9Cancan Zhou0Zhengyuan Feng1Weikun Qian2Zeen Zhu3Ruiqi Cao4Qiqi Wang5Wunai Zhang6Rujuan Liu7Shuai Wu8Jie Hao9Zheng Wang10Qingyong Ma11Zheng Wu12Xuqi Li13Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of General Surgery, Second Affiliated Hospital, Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Pancreatic cancer is a lethal disease with an insidious onset, and little is known about its early molecular events. Here, we found that the sterol regulatory element-binding protein 1 (SREBP1) expression is gradually upregulated during the initiation of pancreatic cancer. Through in vitro 3D culture of pancreatic acinar cells and experiments in LSL-Kras G12D/+ ;Pdx1-Cre (KC) mice, we found that pharmacological inhibition of SREBP1 suppressed pancreatic tumorigenesis. In vitro, either knockdown or pharmacological inhibition of SREBP1 suppressed tumor proliferation but SREBP1 overexpression promoted tumor proliferation. In LSL-Kras G12D/+ ;Trp53 fl/+ ;Pdx1-Cre (KPC) mice, we confirmed the tumor-promoting role of SREBP1 in pancreatic cancer progression. Mechanistically, we revealed SOX9 as a downstream target of SREPB1. SREBP1 inhibition decreased SOX9 expression in both acinar cells and pancreatic cancer cells. Indeed, we identified SREBP1 binding sites in the SOX9 promoter region and reported that SOX9 is transcriptionally regulated by SREBP1. Taken together, our findings demonstrate that SREBP1/SOX9 inhibition suppresses pancreatic cancer initiation and growth, suggesting that SREBP1 could serve as a potential target for cancer screening and treatment.https://doi.org/10.1186/s13062-025-00595-1Pancreatic cancerTumorigenesisTumor growthSREBP1SOX9 |
| spellingShingle | Cancan Zhou Zhengyuan Feng Weikun Qian Zeen Zhu Ruiqi Cao Qiqi Wang Wunai Zhang Rujuan Liu Shuai Wu Jie Hao Zheng Wang Qingyong Ma Zheng Wu Xuqi Li Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9 Biology Direct Pancreatic cancer Tumorigenesis Tumor growth SREBP1 SOX9 |
| title | Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9 |
| title_full | Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9 |
| title_fullStr | Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9 |
| title_full_unstemmed | Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9 |
| title_short | Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9 |
| title_sort | elevated srebp1 accelerates the initiation and growth of pancreatic cancer by targeting sox9 |
| topic | Pancreatic cancer Tumorigenesis Tumor growth SREBP1 SOX9 |
| url | https://doi.org/10.1186/s13062-025-00595-1 |
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