Diagnostic, prognostic and therapeutic implications of carbonic anhydrases in cancer

Proliferating cell nuclear antigen in the cytoplasm interacts with components of glycolysis and cancer

“…Nevertheless, it should be noted that the association of annexin A2 and PCNA was also found by another group [29]. Carbonic anhydrase, which catalyzes reversible hydration of carbon dioxide, is associated with diverse pathological conditions; thus, it has been a target for drug developments for several human diseases, including glaucoma and cancer [38,39]. These data together with our current finding raise the possibility that PCNA may be involved in (preventing) pathological development by binding and modulating carbonic anhydrase.…”

Role of the HBx oncoprotein in carbonic anhydrase 9 induction

“…CA IX is one of the most hypoxia-responsive genes and was proposed to serve as an intrinsic marker of hypoxia [Potter and Harris, 2003]. It catalyzes the reversible conversion of CO 2 to bicarbonate ion and proton like other active carbonic anhydrases, and participates in ion transport and pH control [Svastova et al, 2004].…”

Alternative splicing variant of the hypoxia marker carbonic anhydrase IX expressed independently of hypoxia and tumour phenotype

“…The CA isoforms show remarkable diversity in their enzyme activity, kinetic properties, distribution in tissues, localisation in subcellular compartments and sensitivity to inhibitors. This diversity enables them to fulfill specific roles in metabolically active organs and in various physiological situations .In contrast to the majority of CA isoforms that are mostly present in differentiated cells of the normal tissues, CA IX expression is predominantly associated with a broad range of tumours derived from cells, which contain no or low level of CA IX (Potter and Harris, 2003). The only normal tissues that show moderate-to-abundant expression of CA IX belong to gastrointestinal tract and comprise epithelia of the glandular stomach, small intestine, and gallbladder (Pastorekova et al, 1997).…”

“…The HIF transcription factor significantly changes the expression profile of weakly oxygenated tumour cells by the activation of genes that either support their survival and adaptation to hypoxic stress or lead to their death. As a result, hypoxia selects more aggressive tumour cells with increased capability to invade and metastasise and is therefore inherently associated with bad prognosis and poor response to anticancer therapy (Harris, 2002).Strong induction by HIF, hypoxia-related intratumoral distribution, and the relationship to cancer development and/or treatment outcome predispose CA IX to serve as a surrogate marker of hypoxia with a prognostic value (Potter and Harris, 2003). Moreover, CA IX also appears to play an active role in tumour biology via modulation of cell adhesion and control of pH Svastova et al, 2004;Swietach et al, 2007).…”