ausblenden:
Schlagwörter:
LGALS3BP; cancer biomarker; extracellular matrix; integrin signalling; therapeutic target
Zusammenfassung:
The extracellular matrix protein lectin galactoside-binding soluble 3 binding protein (LGALS3BP) constitutes a negative prognostic
marker of cancer onset and progression with increasing value in clinical application. Since its discovery, however, although the
glycoprotein has been implicated in a growing number of disease-related processes, its actual role and mechanism of action have
remained ambiguous, thus hindering opportunities for therapeutic development. In this study, we have determined that LGALS3BP
constitutes a novel ligand for integrins a1b1, a5b1, avb1 and a6b1 and have identified that these newly established partnerships at the
membrane level are responsible for exerting the molecule’s involvement in cancer through manipulation of multiple canonical
‘outside-in’ integrin signalling events. We demonstrate that LGALS3BP-mediated integrin activation results into signal transmission via
Akt, JNK and the Ras cascade via the Raf-ERK axis while p38 activity is kept at baseline levels. Transient cellular adherence to LGALS3BP
favours survival and proliferation signalling while apoptosis is kept at bay. Sustained cellular exposure to LGALS3BP significantly
supports viability, motility and migration. Importantly, an anti-LGALS3BP antibody, SP2 is capable of impeding these newly defined
LGALS3BP-driven processes without, however, compromising cell viability. These novel findings reveal the mechanism of action of
LGALS3BP during cellular adherence and warrant its further validation as a potential pharmacological target for anticancer therapies.
