Overexpression of pyruvate carboxylase Δs correlated with colorectal cancer progression and supports growth of invasive colon cancer HT-29 cell line

Abstract

© 2020 International Institute of Anticancer Research. All rights reserved. Background/Aim: Pyruvate carboxylase (PC) is a major anaplerotic enzyme for generating oxaloacetate for the TCA cycle and also a key enzyme in gluconeogenesis, de novo fatty acid and amino acid synthesis in normal cells. Recent studies have identified PC overexpression in different cancers, such as breast and lung. However, the involvement of PC in colorectal cancer (CRC) is unclear. Our purpose was to investigate the PC expression levels and its correlations with potentially relevant clinical-pathological parameters in CRC. Materials and Methods: PC expression levels in tissues from 60 Thai CRC patients were investigated by immunohistochemistry while a clonogenic assay was performed for determining cell growth of HT-29 cells with PC knockdown. Results: Our results showed for the first time that high PC expression levels were significantly correlated with late stage of the cancer, perineural invasion and lymph node metastasis. The overexpression of PC was also significantly associated with poor overall and disease-free survival times of CRC patients. In addition, suppression of cancer cell growth was found in PC-deficient cell lines using CRISPR-Cas9. Conclusion: The overexpression levels of PC were correlated with CRC progression and survival times. Therefore, PC might serve as a potential clinical prognostic marker for colorectal cancer.