Carbonic anhydrase III promotes transformation and invasion capability in hepatoma cells through FAK signaling pathway

Abstract

Carbonic anhydrase III (CAIII) is distinguished from the other members of the CA family by low carbon dioxide hydratase activity, resistance to the CA inhibitor acetazolamide, and a predominant expression in the liver of males. In this report the effects of CAIII expression on liver cancer cells invasiveness were explored. Overexpression of CAIII in the HCC cell line SK-Hep1 resulted in increased anchorage-independent growth and invasiveness. And siRNA-mediated silencing of CAIII expression decreased the invasive ability of SK-Hep1 cells. Furthermore, CAIII transfectants showed elevated focal adhesion kinase (FAK) and Src activity. Silencing of FAK expression in CAIII transfectants led to suppression of HCC cell invasion. More importantly, the CAIII transfectants acidified the culture medium at an accelerated speed than the control cells did. Taken together, these data suggest that the CAIII-promoted invasive ability of HCC cells may probably be mediated through, at least in part, the FAK signaling pathway via intracellular and/or extracellular acidification.

Molecular Characterization of EGFR and EGFRvIII Signaling Networks in Human Glioblastoma Tumor Xenografts

“…These findings corroborate the data we present here and, because of its role in GBM invasiveness, highlight GBP1 as a potential therapeutic target in GBM. CAIII belongs to the carbonic anhydrase family of metalloenzymes that catalyze the reversible hydration of carbon dioxide for pH homeostasis (49 independent growth, cell motility, and invasion in hepatocellular carcinoma cell lines through an unknown mechanism (50). Furthermore, CAIII is unique in the carbonic anhydrase family as it has phosphatase activity (with a preference for tyrosine phosphorylation) (49).…”

Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling

“…FAK is known to be important in the regulation of focal adhesion dynamics and disassembly during cell migration (62). It is activated in a range of tumor cells, and its increased activity correlates with the malignancy and invasiveness of human HCC and other tumors (63)(64)(65). Phosphorylation of FAK at Tyr-397 and the subsequent phosphorylation of other focal adhesion complex-associated proteins (e.g., paxillin and p130Cas) are required for focal adhesion formation and cell migration (66).…”

SIRPα1 receptors interfere with the EGFRvIII signalosome to inhibit glioblastoma cell transformation and migration

“…On the other hand, increased FAK expression and activity has been reported to enhance transformation, invasion and malignant tumor phenotype (Benlimame et al, 2005;Madan et al, 2006;Aponte et al, 2008;Dai et al, 2008;Luo et al, 2009). FAK has also been shown to activate the MAPK pathway through multiple pathways, including through the Src/SHP-2/SIRPa1(SHPS-1) axis (Takeda et al, 1998;Tsuda et al, 1998).…”