Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells

Zhe Cheng; Huichao Huang; Maoyu Li; Yongheng Chen

doi:10.1016/j.isci.2023.108645

Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells

iScience. 2023 Dec 6;27(1):108645. doi: 10.1016/j.isci.2023.108645. eCollection 2024 Jan 19.

Authors

Zhe Cheng¹, Huichao Huang², Maoyu Li³, Yongheng Chen³

Affiliations

¹ Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
² Department of Infectious Disease, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
³ Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Abstract

Aerobic glycolysis is a pivotal hallmark of cancers, including colorectal cancer. Evidence shows glycolytic enzymes are regulated by post-translational modifications (PTMs), thereby affecting the Warburg effect and reprograming cancer metabolism. Lysine lactylation is a PTM reported in 2019 in histones. In this study, we identified protein lactylation in FHC cells and SW480 colon cancer cells through mass spectrometry. Totally, 637 lysine lactylation sites in 444 proteins were identified in FHC and SW480 cells. Lactylated proteins were enriched in the glycolysis pathway, and we identified lactylation sites in phosphofructokinase, platelet (PFKP) lysine 688 and aldolase A (ALDOA) lysine 147. We also showed that PFKP lactylation directly attenuated enzyme activity. Collectively, our study presented a resource to investigate proteome-wide lactylation in SW480 cells and found PFKP lactylation led to activity inhibition, indicating that lactic acid and lactylated PFKP may form a negative feedback pathway in glycolysis and lactic acid production.

Keywords: Cancer; Cell biology; Properties of biomolecules; Proteomics.