Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver, ranking third in the overall global cancer-related mortality. A complex interacting network of associated proteins controls HCC growth and progression. Lysophosphatidic acid receptors (LPARs) are commonly overexpressed in HCC. In particular, we recently showed that overexpression of LPAR6 sustains tumorigenesis and growth of HCC and that this is associated with a poor prognosis in patients with HCC. Here, we applied advanced proteomics-based technologies to identify changes in protein expression in HCC cells overexpressing LPAR6 (HLE-LPAR6). We found that a total of 19 proteins were significantly deregulated in these cells, revealing the influence of LPAR6 in modulating the expression of a network of proteins in cancer cells. In particular, we found that overexpression of LPAR6 affects carbohydrate metabolism enzymes (i.e. PGK1, TALDO1, ALDOB and GAPDH enzymes regulating the glycolytic rate) and oxidation-reduction/detoxification proteins (i.e. P4HB, SOD2, LGAS1) in HCC cells, as evaluated by 2D mass spectrometry. Our findings corroborate the role of LPAR6 as the master regulator of tumorigenicity in HCC and highlight biomolecules that can be potentially employed as a biomarker for theranostic purpose
LPAR6 controls a network of proteins that regulate carbohydrate metabolism and oxidation-reduction/detoxification in HCC cells
Rosa Lippolis;
2019
Abstract
Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver, ranking third in the overall global cancer-related mortality. A complex interacting network of associated proteins controls HCC growth and progression. Lysophosphatidic acid receptors (LPARs) are commonly overexpressed in HCC. In particular, we recently showed that overexpression of LPAR6 sustains tumorigenesis and growth of HCC and that this is associated with a poor prognosis in patients with HCC. Here, we applied advanced proteomics-based technologies to identify changes in protein expression in HCC cells overexpressing LPAR6 (HLE-LPAR6). We found that a total of 19 proteins were significantly deregulated in these cells, revealing the influence of LPAR6 in modulating the expression of a network of proteins in cancer cells. In particular, we found that overexpression of LPAR6 affects carbohydrate metabolism enzymes (i.e. PGK1, TALDO1, ALDOB and GAPDH enzymes regulating the glycolytic rate) and oxidation-reduction/detoxification proteins (i.e. P4HB, SOD2, LGAS1) in HCC cells, as evaluated by 2D mass spectrometry. Our findings corroborate the role of LPAR6 as the master regulator of tumorigenicity in HCC and highlight biomolecules that can be potentially employed as a biomarker for theranostic purposeI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
