ALG3 Promotes Peritoneal Metastasis of Ovarian Cancer through Increasing Interaction of α1,3-mannosylated uPAR and ADAM8
Peritoneal metastasis is the main cause of poor prognoses and high mortality in ovarian cancer patients. Abnormal protein glycosylation modification is associated with cancer malignancy. Elevated α1,3-mannosyltransferase 3 (ALG3), which catalyzes the α1,3-mannosylation of glycoproteins, has been fou...
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MDPI AG
2022-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/19/3141 |
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| author | Xinyuan Cui Xiaosong Pei Hao Wang Ping Feng Huamin Qin Shuai Liu Qiu Yan Jiwei Liu |
| author_facet | Xinyuan Cui Xiaosong Pei Hao Wang Ping Feng Huamin Qin Shuai Liu Qiu Yan Jiwei Liu |
| author_sort | Xinyuan Cui |
| collection | DOAJ |
| description | Peritoneal metastasis is the main cause of poor prognoses and high mortality in ovarian cancer patients. Abnormal protein glycosylation modification is associated with cancer malignancy. Elevated α1,3-mannosyltransferase 3 (ALG3), which catalyzes the α1,3-mannosylation of glycoproteins, has been found in some malignant tumors. However, the pathological significance of ALG3 and its regulatory mechanism in ovarian cancer metastasis is unclear. The results showed that the level of ALG3/α1,3-mannosylation was higher in human ovarian cancer tissues compared with normal ovarian tissues, as measured by Lectin chip, Western blot and Lectin blot analyses, as well as ovarian tissue microarray analysis. ALG3 was also correlated with the poor prognosis of ovarian cancer patients, according to survival analysis. The downregulation of ALG3 decreased the proliferation, stemness and peritoneal metastasis of ovarian cancer cells. The increase in urokinase plasminogen activator receptor (uPAR) α1,3-mannosylation catalyzed by ALG3 enhanced urokinase plasminogen activator (uPA)/uPAR activation and the interaction of uPAR with a disintegrin and metalloproteinase 8 (ADAM8), which promoted ovarian cancer peritoneal metastasis via the ADAM8/Ras/ERK pathway. Furthermore, decreased ALG3 suppressed ascites formation and the peritoneal metastasis of ovarian cancer cells in mice. This study highlights ALG3 as a potential diagnostic biomarker and prospective therapeutic target for ovarian cancer. |
| first_indexed | 2024-03-09T21:52:28Z |
| format | Article |
| id | doaj.art-0f250b13e4a64a448fedc8e7c3f8964e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T21:52:28Z |
| publishDate | 2022-10-01 |
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| series | Cells |
| spelling | doaj.art-0f250b13e4a64a448fedc8e7c3f8964e2023-11-23T20:03:30ZengMDPI AGCells2073-44092022-10-011119314110.3390/cells11193141ALG3 Promotes Peritoneal Metastasis of Ovarian Cancer through Increasing Interaction of α1,3-mannosylated uPAR and ADAM8Xinyuan Cui0Xiaosong Pei1Hao Wang2Ping Feng3Huamin Qin4Shuai Liu5Qiu Yan6Jiwei Liu7Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, ChinaLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian Medical University, Dalian 116044, ChinaLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian Medical University, Dalian 116044, ChinaDepartment of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, ChinaDepartment of Pathology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116011, ChinaLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian Medical University, Dalian 116044, ChinaLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian Medical University, Dalian 116044, ChinaDepartment of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, ChinaPeritoneal metastasis is the main cause of poor prognoses and high mortality in ovarian cancer patients. Abnormal protein glycosylation modification is associated with cancer malignancy. Elevated α1,3-mannosyltransferase 3 (ALG3), which catalyzes the α1,3-mannosylation of glycoproteins, has been found in some malignant tumors. However, the pathological significance of ALG3 and its regulatory mechanism in ovarian cancer metastasis is unclear. The results showed that the level of ALG3/α1,3-mannosylation was higher in human ovarian cancer tissues compared with normal ovarian tissues, as measured by Lectin chip, Western blot and Lectin blot analyses, as well as ovarian tissue microarray analysis. ALG3 was also correlated with the poor prognosis of ovarian cancer patients, according to survival analysis. The downregulation of ALG3 decreased the proliferation, stemness and peritoneal metastasis of ovarian cancer cells. The increase in urokinase plasminogen activator receptor (uPAR) α1,3-mannosylation catalyzed by ALG3 enhanced urokinase plasminogen activator (uPA)/uPAR activation and the interaction of uPAR with a disintegrin and metalloproteinase 8 (ADAM8), which promoted ovarian cancer peritoneal metastasis via the ADAM8/Ras/ERK pathway. Furthermore, decreased ALG3 suppressed ascites formation and the peritoneal metastasis of ovarian cancer cells in mice. This study highlights ALG3 as a potential diagnostic biomarker and prospective therapeutic target for ovarian cancer.https://www.mdpi.com/2073-4409/11/19/3141ALG3α1,3-mannosylationuPARADAM8peritoneal metastasisovarian cancer |
| spellingShingle | Xinyuan Cui Xiaosong Pei Hao Wang Ping Feng Huamin Qin Shuai Liu Qiu Yan Jiwei Liu ALG3 Promotes Peritoneal Metastasis of Ovarian Cancer through Increasing Interaction of α1,3-mannosylated uPAR and ADAM8 Cells ALG3 α1,3-mannosylation uPAR ADAM8 peritoneal metastasis ovarian cancer |
| title | ALG3 Promotes Peritoneal Metastasis of Ovarian Cancer through Increasing Interaction of α1,3-mannosylated uPAR and ADAM8 |
| title_full | ALG3 Promotes Peritoneal Metastasis of Ovarian Cancer through Increasing Interaction of α1,3-mannosylated uPAR and ADAM8 |
| title_fullStr | ALG3 Promotes Peritoneal Metastasis of Ovarian Cancer through Increasing Interaction of α1,3-mannosylated uPAR and ADAM8 |
| title_full_unstemmed | ALG3 Promotes Peritoneal Metastasis of Ovarian Cancer through Increasing Interaction of α1,3-mannosylated uPAR and ADAM8 |
| title_short | ALG3 Promotes Peritoneal Metastasis of Ovarian Cancer through Increasing Interaction of α1,3-mannosylated uPAR and ADAM8 |
| title_sort | alg3 promotes peritoneal metastasis of ovarian cancer through increasing interaction of α1 3 mannosylated upar and adam8 |
| topic | ALG3 α1,3-mannosylation uPAR ADAM8 peritoneal metastasis ovarian cancer |
| url | https://www.mdpi.com/2073-4409/11/19/3141 |
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