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Role of BAG3 in cancer progression: A therapeutic opportunity

2017; Elsevier BV; Volume: 78; Linguagem: Inglês

10.1016/j.semcdb.2017.08.049

1096-3634

Margot De Marco, Anna Basile, Vittoria Iorio, Michelina Festa, Antonia Falco, B. Ranieri, Maria Pascale, Gianluca Sala, Paolo Remondelli, Mario Capunzo, Matthew A. Firpo, Raffaele Pezzilli, Liberato Marzullo, Pierpaolo Cavallo, Vincenzo De Laurenzi, Maria Caterina Turco, Alessandra Rosati,

Cellular Mechanics and Interactions

BAG3 is a multifunctional protein that can bind to heat shock proteins (Hsp) 70 through its BAG domain and to other partners through its WW domain, proline-rich (PXXP) repeat and IPV (Ile-Pro-Val) motifs. Its intracellular expression can be induced by stressful stimuli, while is constitutive in skeletal muscle, cardiac myocytes and several tumour types. BAG3 can modulate the levels, localisation or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility. A secreted form of BAG3 has been identified in studies on pancreatic ductal adenocarcinoma (PDAC). Secreted BAG3 can bind to a specific receptor, IFITM2, expressed on macrophages, and induce the release of factors that sustain tumour growth and the metastatic process. BAG3 neutralisation therefore appears to constitute a novel potential strategy in the therapy of PDAC and, possibly, other tumours.