2. Academic Validation
  3. FAM111B enhances glycolysis and promotes metastasis of prostate cancer by upregulating LDHA

FAM111B enhances glycolysis and promotes metastasis of prostate cancer by upregulating LDHA

  • Neoplasia. 2025 Nov:69:101227. doi: 10.1016/j.neo.2025.101227.
Qingliu He 1,  Haoran Li 2,  Yukun Cong 2,  Kang Chen 2,  Lulin Cheng 3,  Fang Lv 2,  Pu Zhang 4,  Yunjie Ju 2,  Zehao Yu 2,  Jinyu Chen 2,  Chuxiong Wang 2,  Yarong Song 2,  Xuechao Li 5,  Liang Chen 6,  Yifei Xing 7
Affiliations

Affiliations

  • 1 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, NO.1277 Jiefang Avenue, Wuhan 430022, China; Department of Urology, The Second Affiliated Hospital of Fujian Medical University, NO. 34 North Zhongshan Road, Quanzhou 362000, China.
  • 2 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, NO.1277 Jiefang Avenue, Wuhan 430022, China.
  • 3 Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
  • 4 Department of Urology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, China.
  • 5 Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China. Electronic address: xuechao_li@yahoo.com.
  • 6 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, NO.1277 Jiefang Avenue, Wuhan 430022, China. Electronic address: 2023xh0053@hust.edu.cn.
  • 7 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, NO.1277 Jiefang Avenue, Wuhan 430022, China. Electronic address: yfxing@hust.edu.cn.
PMID: 40975977 DOI: 10.1016/j.neo.2025.101227
Abstract

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.

Keywords

FAM111B; Glycolysis; LDHA; Metastasis; PCa.

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