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Expression of organic anion transporting polypeptides (OATP) transporters can be modified with potential incidence in cancers, yet they have not been considered in melanoma. Here, we demonstrate transcriptional and protein expression of OATP members in human melanoma cell lines with sodium-independent organic anion uptake activity. Importantly, uptake of different organic anions over 24 h led to a common resistance signal to apoptotic cell death, induced further by cisplatin in 24 h. The mechanism is not dependent on the transport of cisplatin by the OATP, as it is not an OATP substrate. The resistance signal was modulated by PKC, disclosing it as signal mediator. This study suggests that OATP, which can be constantly activated by endobiotics, may contribute to melanoma chemotherapeutic resistance, thereby justifying the development of OATP targeting strategies. [ABSTRACT FROM AUTHOR]

Examines the biogenesis of a major integrin in human colonic adenocarcinoma cell line. Involvement of calnexin at different temperatures; Responsibility for the adhesion of epithelial cells to laminins; Description of the biosynthesis of the integrin.

Background Information: Previous studies have reported that cross-talk between integrins may be an important regulator of integrin-ligand binding and subsequent signalling events that control a variety of cell functions in many tissues. We previously demonstrated that αvβ5/β6 integrin represses α2β1-dependent cell migration. The αv subunits undergo an endoproteolytic cleavage by protein convertases, whose role in tumoral invasion has remained controversial., Results: Inhibition of convertases by the convertase inhibitor α1-PDX (α1-antitrypsin Portland variant), leading to the cell-surface expression of an uncleaved form of the αv integrin, stimulated cell migration toward type I collagen. Under convertase inhibition, α2β1 engagement led to enhanced phosphorylation of both FAK (focal adhesion kinase) and MAPK (mitogen-activated protein kinase). This outside-in signalling stimulation was associated with increased levels of activated β1 integrin located in larger than usual focal-adhesion structures and a cell migration that was independent of the PI3K (phosphoinositide 3-kinase)/Akt (also called protein kinase B) pathway., Conclusions: The increase in cell migration observed upon convertases inhibition appears to be due to the up-regulation of β1 integrins and to their location in larger focal-adhesion structures. The endoproteolytic cleavage of αv subunits is necessary for αvβ5/β6 integrin to control α2β1 function and could thus play an essential role in colon cancer cell migration.