Qingliu He , Haoran Li , Yukun Cong , Kang Chen , Lulin Cheng , Fang Lv , Pu Zhang , Yunjie Ju , Zehao Yu , Jinyu Chen , Chuxiong Wang , Yarong Song , Xuechao Li , Liang Chen , Yifei Xing
{"title":"FAM111B通过上调LDHA促进糖酵解,促进前列腺癌转移","authors":"Qingliu He , Haoran Li , Yukun Cong , Kang Chen , Lulin Cheng , Fang Lv , Pu Zhang , Yunjie Ju , Zehao Yu , Jinyu Chen , Chuxiong Wang , Yarong Song , Xuechao Li , Liang Chen , Yifei Xing","doi":"10.1016/j.neo.2025.101227","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The poor prognosis of metastatic prostate cancer (PCa) poses a major burden on both patients and the healthcare system. FAM111 trypsin-like peptidase B (FAM111B) is related to the development and progression of a wide array of cancers, but its role in PCa remains poorly understood.</div></div><div><h3>Methods</h3><div>Primary cells were extracted from subcutaneous and pulmonary metastatic tumors and were used to verify differences in metastatic potential through wound healing assay, Transwell assay, soft agar colony formation assay, and in vivo pulmonary metastasis reformation assays. The key differentially expressed gene FAM111B related to metastatic prostate cancer (mPCa) was identified through transcriptomic combination analysis, proteomic analysis, quantitative real-time fluorescent polymerase chain reaction and western blot assays. The effect of FAM111B on the glycolytic capacity of PCa cells with high metastatic potential was analyzed by gene enrichment analysis, glucose uptake, lactate and ATP content measurement assays, including glycolytic stress test.</div></div><div><h3>Results</h3><div>FAM111B was highly expressed in metastatic PCa cells and associated with adverse clinical features, which upregulated LDHA to enhance glycolysis. Mechanistically, the expression of P27 was inhibited by a hydrolytic triad coded by the functional coding region of FAM111B, which activated Cyclin-CDKs/RB/E2F1 classical signaling pathway to promote the transcription and protein expression of LDHA.</div></div><div><h3>Conclusions</h3><div>The high expression of FAM111B is associated with adverse clinical features of PCa. FAM111B protein binds to and hydrolyzes P27 protein, which activates Cyclin-CDKs/RB/E2F1 signaling pathway to increase LDHA expression, thereby enhancing the glycolytic ability and ultimately promoting the metastasis of PCa and may potentially serve as new targets for the treatment of metastatic PCa.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101227"},"PeriodicalIF":7.7000,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"FAM111B enhances glycolysis and promotes metastasis of prostate cancer by upregulating LDHA\",\"authors\":\"Qingliu He , Haoran Li , Yukun Cong , Kang Chen , Lulin Cheng , Fang Lv , Pu Zhang , Yunjie Ju , Zehao Yu , Jinyu Chen , Chuxiong Wang , Yarong Song , Xuechao Li , Liang Chen , Yifei Xing\",\"doi\":\"10.1016/j.neo.2025.101227\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>The poor prognosis of metastatic prostate cancer (PCa) poses a major burden on both patients and the healthcare system. FAM111 trypsin-like peptidase B (FAM111B) is related to the development and progression of a wide array of cancers, but its role in PCa remains poorly understood.</div></div><div><h3>Methods</h3><div>Primary cells were extracted from subcutaneous and pulmonary metastatic tumors and were used to verify differences in metastatic potential through wound healing assay, Transwell assay, soft agar colony formation assay, and in vivo pulmonary metastasis reformation assays. The key differentially expressed gene FAM111B related to metastatic prostate cancer (mPCa) was identified through transcriptomic combination analysis, proteomic analysis, quantitative real-time fluorescent polymerase chain reaction and western blot assays. The effect of FAM111B on the glycolytic capacity of PCa cells with high metastatic potential was analyzed by gene enrichment analysis, glucose uptake, lactate and ATP content measurement assays, including glycolytic stress test.</div></div><div><h3>Results</h3><div>FAM111B was highly expressed in metastatic PCa cells and associated with adverse clinical features, which upregulated LDHA to enhance glycolysis. Mechanistically, the expression of P27 was inhibited by a hydrolytic triad coded by the functional coding region of FAM111B, which activated Cyclin-CDKs/RB/E2F1 classical signaling pathway to promote the transcription and protein expression of LDHA.</div></div><div><h3>Conclusions</h3><div>The high expression of FAM111B is associated with adverse clinical features of PCa. FAM111B protein binds to and hydrolyzes P27 protein, which activates Cyclin-CDKs/RB/E2F1 signaling pathway to increase LDHA expression, thereby enhancing the glycolytic ability and ultimately promoting the metastasis of PCa and may potentially serve as new targets for the treatment of metastatic PCa.</div></div>\",\"PeriodicalId\":18917,\"journal\":{\"name\":\"Neoplasia\",\"volume\":\"69 \",\"pages\":\"Article 101227\"},\"PeriodicalIF\":7.7000,\"publicationDate\":\"2025-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neoplasia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1476558625001071\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neoplasia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1476558625001071","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
FAM111B enhances glycolysis and promotes metastasis of prostate cancer by upregulating LDHA
Background
The poor prognosis of metastatic prostate cancer (PCa) poses a major burden on both patients and the healthcare system. FAM111 trypsin-like peptidase B (FAM111B) is related to the development and progression of a wide array of cancers, but its role in PCa remains poorly understood.
Methods
Primary cells were extracted from subcutaneous and pulmonary metastatic tumors and were used to verify differences in metastatic potential through wound healing assay, Transwell assay, soft agar colony formation assay, and in vivo pulmonary metastasis reformation assays. The key differentially expressed gene FAM111B related to metastatic prostate cancer (mPCa) was identified through transcriptomic combination analysis, proteomic analysis, quantitative real-time fluorescent polymerase chain reaction and western blot assays. The effect of FAM111B on the glycolytic capacity of PCa cells with high metastatic potential was analyzed by gene enrichment analysis, glucose uptake, lactate and ATP content measurement assays, including glycolytic stress test.
Results
FAM111B was highly expressed in metastatic PCa cells and associated with adverse clinical features, which upregulated LDHA to enhance glycolysis. Mechanistically, the expression of P27 was inhibited by a hydrolytic triad coded by the functional coding region of FAM111B, which activated Cyclin-CDKs/RB/E2F1 classical signaling pathway to promote the transcription and protein expression of LDHA.
Conclusions
The high expression of FAM111B is associated with adverse clinical features of PCa. FAM111B protein binds to and hydrolyzes P27 protein, which activates Cyclin-CDKs/RB/E2F1 signaling pathway to increase LDHA expression, thereby enhancing the glycolytic ability and ultimately promoting the metastasis of PCa and may potentially serve as new targets for the treatment of metastatic PCa.
期刊介绍:
Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.