Dopamine-induced SULT1A3/4 promotes EMT and cancer stemness in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma has the second highest incidence rate among malignant cancers in China. Hepatocellular carcinoma development is complex because of the metabolism disequilibrium involving SULT1A3/4, a predominant sulfotransferase that metabolizes sulfonic xenobiotics and endogenous catecholamines. However, the correlation between SULT1A3/4 and hepatocellular carcinoma progression is unclear. By utilizing immunofluorescence and immunohistochemical analysis, we found that in nine hepatocellular carcinoma clinical specimens, SULT1A3/4 was abundantly expressed in tumor tissues compared to that in the adjacent tissues. Moreover, liver cancer cells (HepG2, MHCC97-L, and MHCC97-H) had higher basal expression of SULT1A3/4 than immortalized liver cells (L02 and Chang liver). Ultra-high-pressure liquid chromatography-tandem mass spectrometry assay results further revealed that the concentration of dopamine (a substrate of SULT1A3/4) was negatively correlated with SULT1A3/4 protein expression. As a transcriptional regulator of SULT1A3/4 in turn, dopamine was used to induce SULT1A3/4 in vitro. Interestingly, dopamine significantly induced SULT1A3/4 expression in liver cancer HepG2 cells, while decreased that in L02 cells. More importantly, the expression levels of epithelial-mesenchymal transition biomarkers (N-cadherin and vimentin) and cell stemness biomarkers (nanog, sox2, and oct3/4) considerably increased in HepG2 with dopamine-induced SULT1A3/4, whereas in L02, epithelial-mesenchymal transition and cancer stem cell-associated proteins were contrarily decreased. Furthermore, invasion and migration assays further revealed that dopamine-induced SULT1A3/4 dramatically stimulated the metastatic capacity of HepG2 cells. Our results implied that SULT1A3/4 exhibited bidirectional effect on tumor and normal hepatocytes and may thus provide a novel strategy for hepatocellular carcinoma clinical targeting. In addition, SULT1A3/4 re-expression could serve as a biomarker for hepatocellular carcinoma prognosis.

Aquaporin 9 inhibits growth and metastasis of hepatocellular carcinoma cells via Wnt/β-catenin pathway

“…EMT is characterized by the transformation of cell phenotype from epithelial to mesenchymal cells. Various epithelial and mesenchymal markers such as VI, N-cad and E-cad, Slug, Snail and Twist1 are associated with tumor progression [25,26]. In our study, overexpression of AQP9 reduced the invasion and migration activity of HCC cells by down-regulating E-cad and upregulating N-cad and α-SMA, respectively.…”

Propofol‑induced miR‑125a‑5p inhibits the proliferation and metastasis of ovarian cancer by suppressing LIN28B

“…cells were homogenized and sonicated in RIPA buffer (Sigma-Aldrich; Merck KGaA) on ice. Western blotting was conducted according to our previous report (23). determination of protein content: a small amount of the supernatant was taken with a pipette, and the absorbance was measured by a visible spectrophotometer at a wavelength of 590 nm according to the Bradford method.…”

Integrin α7 knockdown suppresses cell proliferation, migration, invasion and endothelium-mesenchymal transformation in hepatocellular carcinoma

“…Just one previous study discloses that ITGA7 promotes OSCC cell migration and invasion, more importantly, ITGA7 also induces EMT in OSCC [5]. Meanwhile, EMT is not only a well-coordinated process touched off by multiple signaling pathways during embryonic development, but also a kind of pathological characteristic in neoplasia and fibrosis, which has been considered as an essential regulator linked to tumor progression and tumor metastasis through accelerating cancer cell invasion and dissemination to distant organs [18][19][20][21]. In order to explore whether ITGA7 influenced EMT in HCC, we further detected E-cadherin and α-SMA expressions, and we found that ITGA7 knockdown increased E-cadherin expression while decreased α-SMA expression in HCC cells.…”