Phosphofructokinase Platelet Overexpression Accelerated Colorectal Cancer Cell Growth and Motility

Tzung-Ju Lu; Yi-Fen Yang; Ching-Feng Cheng; Ya-Ting Tu; Yi-Ru Chen; Ming-Cheng Lee; Kuo-Wang Tsai

doi:10.7150/jca.82738

Phosphofructokinase Platelet Overexpression Accelerated Colorectal Cancer Cell Growth and Motility

J Cancer. 2023 Apr 2;14(6):943-951. doi: 10.7150/jca.82738. eCollection 2023.

Authors

Tzung-Ju Lu¹, Yi-Fen Yang², Ching-Feng Cheng^{3

4

5}, Ya-Ting Tu⁶, Yi-Ru Chen⁶, Ming-Cheng Lee⁶, Kuo-Wang Tsai^{6

7}

Affiliations

¹ Division of Colon and Rectal Surgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
² Pulmonary function Laboratory, Division of Pulmonary Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital.
³ Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan.
⁴ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
⁵ Department of Pediatrics, Tzu Chi University, Hualien, Taiwan.
⁶ Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.
⁷ Department of Nursing, Cardinal Tien Junior College of Healthcare and Management, Taiwan.

Abstract

Background: Glycolysis is a glucose metabolism pathway that generates the high-energy compound adenosine triphosphate, which supports cancer cell growth. Phosphofructokinase platelet (PFKP) plays a crucial role in glycolysis regulation and is involved in human cancer progression. However, the biological function of PFKP remains unclear in colorectal cancer (CRC). Methods: We analyzed the expression levels of PFKF in colon cancer cells and clinical samples using real-time PCR and western blot techniques. To determine the clinical significance of PFKP expression in colorectal cancer (CRC), we analyzed public databases. In addition, we conducted in vitro assays to investigate the effects of PFKP on cell growth, cell cycle, and motility. Results: An analysis by the Cancer Genome Atlas database revealed that PFKP was significantly overexpressed in CRC. We examined the levels of PFKP mRNA and protein, revealing that PFKP expression was significantly increased in CRC. The results of the univariate Cox regression analysis showed that high PFKP expression was linked to worse disease-specific survival (DSS) and overall survival (OS) [DSS: crude hazard ratio (CHR) = 1.84, 95% confidence interval (CI): 1.01-3.36, p = 0.047; OS: CHR=1.91, 95% CI: 1.06-3.43, p = 0.031]. Multivariate Cox regression analysis revealed that high PFKP expression was an independent prognostic biomarker for the DSS and OS of patients with CRC (DSS: adjusted HR = 2.07, 95% CI: 1.13-3.79, p = 0.018; AHR = 2.34, 95% CI: 1.29-4.25, p = 0.005). PFKP knockdown reduced the proliferation, colony formation, and invasion of CRC cells. In addition, the knockdown induced cell cycle arrest at the G0/G1 phase by impairing cell cycle-related protein expression. Conclusion: Overexpression of PFKP contributes to the growth and invasion of CRC by regulating cell cycle progression. PFKP expression can serve as a valuable molecular biomarker for cancer prognosis and a potential therapeutic target for treating CRC.

Keywords: colorectal cancer; metastasis; phosphofructokinase platelet.