Characterization of the role of extracellular Morgana in cell migration

Chaperone proteins facilitate protein folding, aggregation, and degradation. Although most functions are exerted in the cytoplasm, recent lines of evidence revealed that chaperones are released in the extracellular milieu, when an environmental stress occurs. The 90-kDa heat shock protein HSP90 is an abundant chaperone protein highly conserved from bacteria to humans. The surprising observation of HSP90 secretion set the groundwork for further investigation on its extracellular function. On one hand, it was characterized as an unconventional wound-healing factor, which promotes tissue repair. On the other, when secreted by cancer cells, extracellular HSP90 emerged as a pivotal regulator of tumor cell motility, invasion and metastasis. Morgana, also known as CHP-1, is a highly conserved and ubiquitously expressed protein with chaperone and co-chaperone functions. We demonstrated that Morgana is actively and unconventionally secreted by Triple Negative Breast Cancer cell lines. Once outside, extracellular Morgana (eMorgana) promotes cancer cell migration in an autocrine manner, binding to TLR2 and TLR4. Besides its pro-tumorigenic function, eMorgana is secreted by mouse embryonic fibroblasts, and is effective in promoting their pro-motility phenotype. This observation encourages further investigations to deepen eMorgana dichotomous role as a sinister effector of tumor progression and as a likely facilitator of wound healing process. Importantly in cancer context, our data are relevant findings in the understanding of the potential clinical utility of eMorgana, as diagnostic or prognostic biomarker or as therapeutic target.