Loss of tumor suppressive properties of lipid metabolism enzyme CPT2 in ovarian carcinoma: Comment on “CPT2 down-regulation promotes tumor growth and metastasis through inducing ROS/NFκB pathway in ovarian cancer” by Zhang et al.

Abstract

Lipid metabolism is an essential process in cancer growth and progression. It is highly relevant in tumors with an adipocyte-rich microenvironment, such as ovarian carcinoma (OC). Carnitine palmitoyltransferase 2 (CPT2) is a key enzyme in fatty acid oxidation (FAO) that functions as a tumor suppressor in OC. Downregulation of CPT2 is reportedly associated with poor prognosis of OC patients. At the cellular level, low CPT2 translates into reduced NADPH level and unopposed reactive-oxygen species (ROS)/nuclear factor kappa B (NFκB) signaling which are paralleled by induction of mesenchymal mediators, invasion and metastasis. While strategies to propagate the tumor suppressive properties of CPT2 have yet to be developed, a comprehensive approach of co-assessment and co-targeting of CPT2 and its family member CPT1, or/and other key FAO players with FAO-specific inhibitors or/and less specific inhibitors (e.g. targeting NFκB, STAT3) is worth pursuing to improve understanding of the metabolic aspects of OC and develop a lipid metabolism-centered therapeutic strategy that can benefit OC patients.

The Role of Oxidative Stress in Tumorigenesis and Progression

“…For example, high levels of ROS in tumor cells activate NF-κB, promoting transcription factor (Snail) expression, downregulating epithelial calmodulin (E-cadherin), and promoting the expression of neural calmodulin and waveform protein, which leads to disruption of cell–cell junctions and triggers the EMT process, stimulating tumor cell metastasis [ 95 ]. Furthermore, the downregulation of carnitine palmitoyltransferase 2 (CPT2) induces the ROS/NF-κB pathway in ovarian cancer to promote tumor growth and metastasis [ 96 ].…”

Adipocyte‑rich microenvironment promotes chemoresistance via upregulation of peroxisome proliferator‑activated receptor gamma/ABCG2 in epithelial ovarian cancer

“…Ovarian cancer (OVCA), a representative adipocyte-rich associated cancer ( 7 , 8 ), is the most lethal gynecological malignancy, with a 5-year survival rate of 48% ( 9 ). Of OVCA cases, ~90% are epithelial ovarian cancer (EOC) in terms of histological type and the most common subtype of EOC is high-grade serous ovarian carcinoma (HGSOC; 70% of cases) and it also has the worst prognosis ( 10 ).…”