The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues

Lin Li; Siyuan Cheng; Yunshin Yeh; Yingli Shi; Nikayla Henderson; David Price; Xin Gu; Xiuping Yu

doi:10.3389/fonc.2024.1392085

The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues

Front Oncol. 2024 Apr 12:14:1392085. doi: 10.3389/fonc.2024.1392085. eCollection 2024.

Authors

Lin Li^{1

2}, Siyuan Cheng^{1

2}, Yunshin Yeh³, Yingli Shi^{1

2}, Nikayla Henderson¹, David Price⁴, Xin Gu⁵, Xiuping Yu^{1

2

4}

Affiliations

¹ Department of Biochemistry and Molecular Biology, LSU Health Sciences Center at Shreveport, Shreveport, LA, United States.
² Feist-Weiller Cancer Center, LSU Health Sciences Center at Shreveport, Shreveport, LA, United States.
³ Pathology & Laboratory Medicine Service, Overton Brooks VA Medical Center, Shreveport, LA, United States.
⁴ Department of Urology, LSU Health Sciences Center at Shreveport, Shreveport, LA, United States.
⁵ Department of Pathology, LSU Health Sciences Center at Shreveport, Shreveport, LA, United States.

Abstract

Background: Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer (PCa). However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2. The expression pattern of PKM1 and PKM2 in NEPCa remains unknown.

Methods: In this study, we used immunohistochemistry, immunofluorescence staining, and bioinformatics analysis to examine the expression of PKM1 and PKM2 in mouse and human prostatic tissues.

Results: We found that PKM2 was the predominant isoform expressed throughout prostate development and PCa progression, with slightly reduced expression in murine NEPCa. PKM1 was mostly expressed in stromal cells but low-level PKM1 was also detected in prostate basal epithelial cells. Its expression was absent in the majority of prostate adenocarcinoma (AdPCa) specimens but present in a subset of NEPCa. Additionally, we evaluated the mRNA levels of ten PKM isoforms that express exon 9 (PKM1-like) or exon 10 (PKM2-like). Some of these isoforms showed notable expression levels in PCa cell lines and human PCa specimens.

Discussion: Our study characterized the expression pattern of PKM1 and PKM2 in prostatic tissues including developing, benign, and cancerous prostate. These findings lay the groundwork for understanding the metabolic changes in different PCa subtypes.

Keywords: PKM1; PKM2; metabolism; neuroendocrine; prostate cancer.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by NIH R01 CA226285, LSU Collaborative Cancer Research Initiative, LSU Health Shreveport Office of Research, and LSU Health Shreveport FWCC Stimulus grants to XY, LSU Health Shreveport FWCC Carroll Feist predoctoral Fellowship to LL, and LSU Health Shreveport FWCC Carroll Feist postdoctoral Fellowship to SC.