Melanophilin-induced primary cilia promote pancreatic cancer metastasis
Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors because of its high metastatic ability. The glutamine (Gln)-deficient microenvironment contributes to PDAC metastasis; however, the underlying molecular mechanisms remain unclear. Here, we demonstrated that melanoph...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07344-2 |
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| author | Yu-Ying Chao Ruei-Ci Lin Ping-Jui Su Chu-An Wang Ting-Yuan Tu Ya-Chin Hou Yi-Tzui Tsai I-Chen Peng Shaw-Jenq Tsai Yan-Shen Shan Chia-Yih Wang |
| author_facet | Yu-Ying Chao Ruei-Ci Lin Ping-Jui Su Chu-An Wang Ting-Yuan Tu Ya-Chin Hou Yi-Tzui Tsai I-Chen Peng Shaw-Jenq Tsai Yan-Shen Shan Chia-Yih Wang |
| author_sort | Yu-Ying Chao |
| collection | DOAJ |
| description | Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors because of its high metastatic ability. The glutamine (Gln)-deficient microenvironment contributes to PDAC metastasis; however, the underlying molecular mechanisms remain unclear. Here, we demonstrated that melanophilin (MLPH) promotes PDAC metastasis by inducing the regrowth of primary cilia. Using RNA sequencing, we found that MLPH was upregulated in Gln-deficient conditions. MLPH facilitated PDAC metastasis in vitro and in vivo. Clinically, high MLPH expression is positively correlated with metastasis and poor PDAC prognosis. MLPH localized to the centrosome and facilitated the regrowth of primary cilia. The primary ciliogenesis upregulated phospholipase C γ-1 (PLCG1) to promote PDAC metastasis. Interestingly, PLCG1 was localized to the primary cilia, and depletion of PLCG1 alleviated primary ciliogenesis, suggesting a feedforward role for PLCG1 in mediating primary ciliogenesis. Thus, our study revealed a novel function of the MLPH-primary cilia-PLCG1 axis in facilitating PDAC metastasis under Gln deficiency both in vitro and in vivo. |
| format | Article |
| id | doaj-art-52a0097f30524bb9af516178d4794929 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-52a0097f30524bb9af516178d47949292025-01-19T12:40:41ZengNature Publishing GroupCell Death and Disease2041-48892025-01-0116111410.1038/s41419-025-07344-2Melanophilin-induced primary cilia promote pancreatic cancer metastasisYu-Ying Chao0Ruei-Ci Lin1Ping-Jui Su2Chu-An Wang3Ting-Yuan Tu4Ya-Chin Hou5Yi-Tzui Tsai6I-Chen Peng7Shaw-Jenq Tsai8Yan-Shen Shan9Chia-Yih Wang10Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityDivision of General Surgery, Department of Surgery, National Cheng Kung University HospitalInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityDepartment of Biomedical Engineering, National Cheng Kung UniversityInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityDepartment of Physiology, College of Medicine, National Cheng Kung UniversityDepartment of Life Sciences, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityAbstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors because of its high metastatic ability. The glutamine (Gln)-deficient microenvironment contributes to PDAC metastasis; however, the underlying molecular mechanisms remain unclear. Here, we demonstrated that melanophilin (MLPH) promotes PDAC metastasis by inducing the regrowth of primary cilia. Using RNA sequencing, we found that MLPH was upregulated in Gln-deficient conditions. MLPH facilitated PDAC metastasis in vitro and in vivo. Clinically, high MLPH expression is positively correlated with metastasis and poor PDAC prognosis. MLPH localized to the centrosome and facilitated the regrowth of primary cilia. The primary ciliogenesis upregulated phospholipase C γ-1 (PLCG1) to promote PDAC metastasis. Interestingly, PLCG1 was localized to the primary cilia, and depletion of PLCG1 alleviated primary ciliogenesis, suggesting a feedforward role for PLCG1 in mediating primary ciliogenesis. Thus, our study revealed a novel function of the MLPH-primary cilia-PLCG1 axis in facilitating PDAC metastasis under Gln deficiency both in vitro and in vivo.https://doi.org/10.1038/s41419-025-07344-2 |
| spellingShingle | Yu-Ying Chao Ruei-Ci Lin Ping-Jui Su Chu-An Wang Ting-Yuan Tu Ya-Chin Hou Yi-Tzui Tsai I-Chen Peng Shaw-Jenq Tsai Yan-Shen Shan Chia-Yih Wang Melanophilin-induced primary cilia promote pancreatic cancer metastasis Cell Death and Disease |
| title | Melanophilin-induced primary cilia promote pancreatic cancer metastasis |
| title_full | Melanophilin-induced primary cilia promote pancreatic cancer metastasis |
| title_fullStr | Melanophilin-induced primary cilia promote pancreatic cancer metastasis |
| title_full_unstemmed | Melanophilin-induced primary cilia promote pancreatic cancer metastasis |
| title_short | Melanophilin-induced primary cilia promote pancreatic cancer metastasis |
| title_sort | melanophilin induced primary cilia promote pancreatic cancer metastasis |
| url | https://doi.org/10.1038/s41419-025-07344-2 |
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