TY - JOUR
T1 - Choline metabolism alteration
T2 - A focus on ovarian cancer
AU - Bagnoli, Marina
AU - Granata, Anna
AU - Nicoletti, Roberta
AU - Krishnamachary, Balaji
AU - Bhujwalla, Zaver M.
AU - Canese, Rossella
AU - Podo, Franca
AU - Canevari, Silvana
AU - Iorio, Egidio
AU - Mezzanzanica, Delia
N1 - Funding Information:
The authors are grateful to the Associazione Italiana per la Ricerca sul Cancro (AIRC, IG-9147, IG-12976, and IG-17475) and to the Ministero della Salute grant RF-2010-2313497 for partially supporting these studies.
Publisher Copyright:
© 2016 Bagnoli, Granata, Nicoletti, Krishnamachary, Bhujwalla, Canese, Podo, Canevari, Iorio and Mezzanzanica.
PY - 2016/6/22
Y1 - 2016/6/22
N2 - Compared with normal differentiated cells, cancer cells require a metabolic reprograming to support their high proliferation rates and survival. Aberrant choline metabolism is a fairly new metabolic hallmark reflecting the complex reciprocal interactions between oncogenic signaling and cellular metabolism. Alterations of the involved metabolic network may be sustained by changes in activity of several choline transporters as well as of enzymes such as choline kinase-alpha (ChoK-α) and phosphatidylcholine-specific phospholipases C and D. Of note, the net outcome of these enzymatic alterations is an increase of phosphocholine and total choline-containing compounds, a "cholinic phenotype" that can be monitored in cancer by magnetic resonance spectroscopy. This review will highlight the molecular basis for targeting this pathway in epithelial ovarian cancer (EOC), a highly heterogeneous and lethal malignancy characterized by late diagnosis, frequent relapse, and development of chemoresistance. Modulation of ChoK-α expression impairs only EOC but not normal ovarian cells, thus supporting the hypothesis that "cholinic phenotype" is a peculiar feature of transformed cells and indicating ChoK-α targeting as a novel approach to improve efficacy of standard EOC chemotherapeutic treatments.
AB - Compared with normal differentiated cells, cancer cells require a metabolic reprograming to support their high proliferation rates and survival. Aberrant choline metabolism is a fairly new metabolic hallmark reflecting the complex reciprocal interactions between oncogenic signaling and cellular metabolism. Alterations of the involved metabolic network may be sustained by changes in activity of several choline transporters as well as of enzymes such as choline kinase-alpha (ChoK-α) and phosphatidylcholine-specific phospholipases C and D. Of note, the net outcome of these enzymatic alterations is an increase of phosphocholine and total choline-containing compounds, a "cholinic phenotype" that can be monitored in cancer by magnetic resonance spectroscopy. This review will highlight the molecular basis for targeting this pathway in epithelial ovarian cancer (EOC), a highly heterogeneous and lethal malignancy characterized by late diagnosis, frequent relapse, and development of chemoresistance. Modulation of ChoK-α expression impairs only EOC but not normal ovarian cells, thus supporting the hypothesis that "cholinic phenotype" is a peculiar feature of transformed cells and indicating ChoK-α targeting as a novel approach to improve efficacy of standard EOC chemotherapeutic treatments.
KW - Antioxidant defense
KW - Choline kinase
KW - Ovarian cancer
KW - Phosphocholine metabolism
KW - Reversal of drug resistance
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U2 - 10.3389/fonc.2016.00153
DO - 10.3389/fonc.2016.00153
M3 - Short survey
C2 - 27446799
AN - SCOPUS:84982854094
SN - 2234-943X
VL - 6
JO - Frontiers in Oncology
JF - Frontiers in Oncology
IS - JUN
M1 - 153
ER -