TCP1 promotes the progression of malignant tumours by stabilizing c-Myc through the AKT/GSK-3β and ERK signalling pathways
Abstract The chaperonin tailless complex polypeptide 1 (TCP1) is a key subunit of chaperonin containing TCP1 (CCT) that regulates the folding and stability of proteins during cancer progression. Here, the prognostic significance of TCP1 was explored mainly in patients with hepatocellular carcinoma (...
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07867-6 |
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| author | Hekun Liu Linying Chen Yuwen Chen Yiyi Jin Xiance Chen Nengjun Ma Fan Yang Huixia Bi Xinxin Wen Shenmin Xu Juan Chen Yanping Lin Yinghong Yang Yong Wu Yuanzhong Chen |
| author_facet | Hekun Liu Linying Chen Yuwen Chen Yiyi Jin Xiance Chen Nengjun Ma Fan Yang Huixia Bi Xinxin Wen Shenmin Xu Juan Chen Yanping Lin Yinghong Yang Yong Wu Yuanzhong Chen |
| author_sort | Hekun Liu |
| collection | DOAJ |
| description | Abstract The chaperonin tailless complex polypeptide 1 (TCP1) is a key subunit of chaperonin containing TCP1 (CCT) that regulates the folding and stability of proteins during cancer progression. Here, the prognostic significance of TCP1 was explored mainly in patients with hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). We showed that TCP1 expression was significantly greater in clinically malignant tumour tissues than in normal tissues and that high TCP1 expression was associated with poor prognosis. TCP1 suppression not only decreased the proliferation and invasion of cancer cells in vitro but also inhibited tumour growth and metastasis in vivo. The underlying mechanisms were determined by ubiquitination assays and Co-IP (Co-Immunoprecipitation) experiments, and it was found that TCP1 regulated the stability of c-Myc through the RAC-alpha serine/threonine-protein kinase (AKT) /Glycogen synthase kinase 3β (GSK-3β) and extracellular regulated protein kinases (ERK) signalling pathways. Moreover, TCP1 knock-in (TCP1-KI) dramatically promoted the occurrence of diethylnitrosamine (DEN) -induced primary HCC in mice. Our results highlight the critical role of TCP1 in HCC and PDAC and reveal a novel mechanism to suppress HCC and PDAC by targeting c-Myc via the TCP1-induced promotion of the AKT/GSK-3β and ERK signalling pathways. TCP1 is able to modulate the stability of target proteins by multiple pathways, thus promoting the progression of HCC and PDAC. Our study identifies TCP1 as a prognostic novel marker and therapeutic target of HCC and PDAC. |
| format | Article |
| id | doaj-art-fd8964ea86d642a3ab8202c463f8e4db |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-fd8964ea86d642a3ab8202c463f8e4db2025-08-20T02:25:41ZengNature PortfolioCommunications Biology2399-36422025-04-018111310.1038/s42003-025-07867-6TCP1 promotes the progression of malignant tumours by stabilizing c-Myc through the AKT/GSK-3β and ERK signalling pathwaysHekun Liu0Linying Chen1Yuwen Chen2Yiyi Jin3Xiance Chen4Nengjun Ma5Fan Yang6Huixia Bi7Xinxin Wen8Shenmin Xu9Juan Chen10Yanping Lin11Yinghong Yang12Yong Wu13Yuanzhong Chen14Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, the First Affiliated Hospital of Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityFujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical UniversityDepartment of Pathology, Fujian Medical University Union HospitalFujian Institute of Haematology, Fujian Key Laboratory on Haematology, Fujian Medical University Union HospitalFujian Institute of Haematology, Fujian Key Laboratory on Haematology, Fujian Medical University Union HospitalAbstract The chaperonin tailless complex polypeptide 1 (TCP1) is a key subunit of chaperonin containing TCP1 (CCT) that regulates the folding and stability of proteins during cancer progression. Here, the prognostic significance of TCP1 was explored mainly in patients with hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). We showed that TCP1 expression was significantly greater in clinically malignant tumour tissues than in normal tissues and that high TCP1 expression was associated with poor prognosis. TCP1 suppression not only decreased the proliferation and invasion of cancer cells in vitro but also inhibited tumour growth and metastasis in vivo. The underlying mechanisms were determined by ubiquitination assays and Co-IP (Co-Immunoprecipitation) experiments, and it was found that TCP1 regulated the stability of c-Myc through the RAC-alpha serine/threonine-protein kinase (AKT) /Glycogen synthase kinase 3β (GSK-3β) and extracellular regulated protein kinases (ERK) signalling pathways. Moreover, TCP1 knock-in (TCP1-KI) dramatically promoted the occurrence of diethylnitrosamine (DEN) -induced primary HCC in mice. Our results highlight the critical role of TCP1 in HCC and PDAC and reveal a novel mechanism to suppress HCC and PDAC by targeting c-Myc via the TCP1-induced promotion of the AKT/GSK-3β and ERK signalling pathways. TCP1 is able to modulate the stability of target proteins by multiple pathways, thus promoting the progression of HCC and PDAC. Our study identifies TCP1 as a prognostic novel marker and therapeutic target of HCC and PDAC.https://doi.org/10.1038/s42003-025-07867-6 |
| spellingShingle | Hekun Liu Linying Chen Yuwen Chen Yiyi Jin Xiance Chen Nengjun Ma Fan Yang Huixia Bi Xinxin Wen Shenmin Xu Juan Chen Yanping Lin Yinghong Yang Yong Wu Yuanzhong Chen TCP1 promotes the progression of malignant tumours by stabilizing c-Myc through the AKT/GSK-3β and ERK signalling pathways Communications Biology |
| title | TCP1 promotes the progression of malignant tumours by stabilizing c-Myc through the AKT/GSK-3β and ERK signalling pathways |
| title_full | TCP1 promotes the progression of malignant tumours by stabilizing c-Myc through the AKT/GSK-3β and ERK signalling pathways |
| title_fullStr | TCP1 promotes the progression of malignant tumours by stabilizing c-Myc through the AKT/GSK-3β and ERK signalling pathways |
| title_full_unstemmed | TCP1 promotes the progression of malignant tumours by stabilizing c-Myc through the AKT/GSK-3β and ERK signalling pathways |
| title_short | TCP1 promotes the progression of malignant tumours by stabilizing c-Myc through the AKT/GSK-3β and ERK signalling pathways |
| title_sort | tcp1 promotes the progression of malignant tumours by stabilizing c myc through the akt gsk 3β and erk signalling pathways |
| url | https://doi.org/10.1038/s42003-025-07867-6 |
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