CD38 is involved in cell energy metabolism via activating the PI3K/AKT/mTOR signaling pathway in cervical cancer cells

• Published in: International journal of oncology Vol. 57; no. 1; pp. 338 - 354
• Main Authors: Liao, Shan, Liang, Lin, Yue, Chunxue, He, Junyu, He, Zhengxi, Jin, Xi, Luo, Gengqiu, Zhou, Yanhong
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.07.2020; Spandidos Publications UK Ltd
• Subjects: ADP-ribosyl Cyclase 1 - metabolism; Cancer cells; Cancer treatment; Cell adhesion & migration; Cell culture; Cell growth; Cervical cancer; EDTA; Energy Metabolism - drug effects; Energy Metabolism - physiology; Female; Glucose; Health aspects; HeLa Cells; Humans; International economic relations; Kinases; Laboratories; Liquid chromatography; Mass spectrometry; Membrane Glycoproteins - metabolism; Metabolism; Metabolites; Peptides; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Scientific equipment industry; Signal transduction; Signal Transduction - drug effects; Sirolimus - pharmacology; Sirolimus - therapeutic use; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - pathology; United States; China
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2020.5040

In contrast to normal cells, cancer cells typically undergo metabolic reprogramming. Studies have shown that oncogenes play an important role in this metabolic reprogramming. CD38 is a multifunctional transmembrane protein that is expressed abnormally in a variety of tumor types. To investigate the effect and possible mechanism of CD38 in cervical cancer cells and to provide a new therapeutic target for the treatment of cervical cancer, the present study identified that CD38 is involved in regulating cell metabolism in cervical cancer cells. Liquid chromatography‑tandem mass spectrometry and bioinformatic analyses revealed that differentially abundant proteins in CD38‑overexpressed cervical cancer cells (CaSki‑CD38 and HeLa‑CD38) are predominantly involved in glycolytic pathways, oxidative phosphorylation and the NAD/NADH metabolic process. Further experiments using an ATP test kit and lactate test kit revealed that CD38 promotes glucose consumption, increases lactate accumulation and increases ATP production. In addition, CD38 increases the phosphorylation of phosphatidylserine/threonine kinase (AKT), mechanistic target of rapamycin (mTOR) and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K), which play a key role in tumor metabolism. Furthermore, it was found that the energy metabolism of cervical cancer cells was inhibited following treatment with the mTOR inhibitor rapamycin. In conclusion, the results of the present study suggested that CD38 regulates the metabolism of cervical cancer cells by regulating the PI3K/AKT/mTOR pathway, which may be a candidate target for the treatment of cervical cancer.