ERBB4 selectively amplifies TGF-β pro-metastatic responses
Summary: Transforming growth factor β (TGF-β) is well known to play paradoxical roles in tumorigenesis as it has both growth-inhibitory and pro-metastatic effects. However, the underlying mechanisms of how TGF-β drives the opposing responses remain largely unknown. Here, we report that ERBB4, a memb...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015614 |
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| author | Peihong Luo Huanyu Hong Baoling Zhang Jie Li Shuyi Zhang Chaomin Yue Jin Cao Jia Wang Yuhan Dai Qingqing Liao Pinglong Xu Bing Yang Xia Liu Xia Lin Yi Yu Xin-Hua Feng |
| author_facet | Peihong Luo Huanyu Hong Baoling Zhang Jie Li Shuyi Zhang Chaomin Yue Jin Cao Jia Wang Yuhan Dai Qingqing Liao Pinglong Xu Bing Yang Xia Liu Xia Lin Yi Yu Xin-Hua Feng |
| author_sort | Peihong Luo |
| collection | DOAJ |
| description | Summary: Transforming growth factor β (TGF-β) is well known to play paradoxical roles in tumorigenesis as it has both growth-inhibitory and pro-metastatic effects. However, the underlying mechanisms of how TGF-β drives the opposing responses remain largely unknown. Here, we report that ERBB4, a member of the ERBB receptor tyrosine kinase family, specifically promotes TGF-β′s metastatic response but not its anti-growth response. ERBB4 directly phosphorylates Tyr162 in the linker region of SMAD4, which enables SMAD4 to achieve a higher DNA-binding ability and potentiates TGF-β-induced gene transcription associated with epithelial-to-mesenchymal transition (EMT), cell migration, and invasion without affecting the genes involved in growth inhibition. These selective effects facilitate lung cancer metastasis in mouse models. This discovery sheds light on the previously unrecognized role of SMAD4 as a substrate of ERBB4 and highlights the selective involvement of the ERBB4-SMAD4 regulatory axis in tumor metastasis. |
| format | Article |
| id | doaj-art-6d47d118297f475cae6c9234785c4ef7 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-6d47d118297f475cae6c9234785c4ef72025-01-24T04:44:59ZengElsevierCell Reports2211-12472025-02-01442115210ERBB4 selectively amplifies TGF-β pro-metastatic responsesPeihong Luo0Huanyu Hong1Baoling Zhang2Jie Li3Shuyi Zhang4Chaomin Yue5Jin Cao6Jia Wang7Yuhan Dai8Qingqing Liao9Pinglong Xu10Bing Yang11Xia Liu12Xia Lin13Yi Yu14Xin-Hua Feng15MOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang 311215, ChinaDepartment of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, China; Corresponding authorMOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, China; The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China; Corresponding authorSummary: Transforming growth factor β (TGF-β) is well known to play paradoxical roles in tumorigenesis as it has both growth-inhibitory and pro-metastatic effects. However, the underlying mechanisms of how TGF-β drives the opposing responses remain largely unknown. Here, we report that ERBB4, a member of the ERBB receptor tyrosine kinase family, specifically promotes TGF-β′s metastatic response but not its anti-growth response. ERBB4 directly phosphorylates Tyr162 in the linker region of SMAD4, which enables SMAD4 to achieve a higher DNA-binding ability and potentiates TGF-β-induced gene transcription associated with epithelial-to-mesenchymal transition (EMT), cell migration, and invasion without affecting the genes involved in growth inhibition. These selective effects facilitate lung cancer metastasis in mouse models. This discovery sheds light on the previously unrecognized role of SMAD4 as a substrate of ERBB4 and highlights the selective involvement of the ERBB4-SMAD4 regulatory axis in tumor metastasis.http://www.sciencedirect.com/science/article/pii/S2211124724015614CP: Cancer |
| spellingShingle | Peihong Luo Huanyu Hong Baoling Zhang Jie Li Shuyi Zhang Chaomin Yue Jin Cao Jia Wang Yuhan Dai Qingqing Liao Pinglong Xu Bing Yang Xia Liu Xia Lin Yi Yu Xin-Hua Feng ERBB4 selectively amplifies TGF-β pro-metastatic responses Cell Reports CP: Cancer |
| title | ERBB4 selectively amplifies TGF-β pro-metastatic responses |
| title_full | ERBB4 selectively amplifies TGF-β pro-metastatic responses |
| title_fullStr | ERBB4 selectively amplifies TGF-β pro-metastatic responses |
| title_full_unstemmed | ERBB4 selectively amplifies TGF-β pro-metastatic responses |
| title_short | ERBB4 selectively amplifies TGF-β pro-metastatic responses |
| title_sort | erbb4 selectively amplifies tgf β pro metastatic responses |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015614 |
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