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An emerging role for BAG3 in gynaecological malignancies

Abstract

BAG3, a member of the BAG family of co-chaperones, is a multidomain protein with a role in several cellular processes, including the control of apoptosis, autophagy and cytoskeletal dynamics. The expression of bag3 is negligible in most cells but can be induced by stress stimuli or malignant transformation. In some tumours, BAG3 has been reported to promote cell survival and resistance to therapy. The expression of BAG3 has been documented in ovarian, endometrial and cervical cancers, and studies have revealed biochemical and functional connections of BAG3 with proteins involved in the survival, invasion and resistance to therapy of these malignancies. BAG3 expression has also been shown to correlate with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix. Some aspects of BAG3 activity, such as its biochemical and functional interaction with the human papillomavirus proteins, could help in our understanding of the mechanisms of oncogenesis induced by the virus. This review aims to highlight the potential value of BAG3 studies in the field of gynaecological tumours.

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Fig. 1: BAG3 structural domains/motifs involved in the regulatory protein–protein interactions of major cellular pathways.
Fig. 2: BAG3 interactors in apoptosis.
Fig. 3: Paracrine loop operated by cancer cell-secreted BAG3 on macrophages surrounding the tumour.
Fig. 4: BAG3 interactors in cancer.
Fig. 5: Cellular processes upregulated by BAG3 expression in gynaecological malignancies.
Fig. 6: Mature miRNAs derive from longer double-stranded primary transcripts (pri-miRNA), processed in the nucleus and folded in a hairpin loop structure (pre-miRNA).

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M.D.M., A.F., R.I., A.R., A.R., M.C.T. and L.M. acquired the literature and data, designed and wrote the paper. A.M., M.G., M.C. and V.N.U. contributed to the concept and design of the paper. M.D.M., G.G., F.D.C., M.C., M.C.T. and L.M. revised the paper and figures. All authors critically read and approved the manuscript being submitted.

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Correspondence to Maria Caterina Turco.

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M.D.M., A.F., A.R., M.C.T. and L.M. are shareholders of BIOUNIVERSA s.r.l.. The remaining authors declare no competing interests.

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This work was supported in part by Associazione Italiana per la Ricerca sul Cancro (AIRC IG 18534) to M.C.T. and in part by POR CAMPANIA FESR 2014–2020 “SYSTEM INNOVATION FOR CANCER EARLY DIAGNOSIS SICED” to M.L., A.R. and M.C.T.

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De Marco, M., Falco, A., Iaccarino, R. et al. An emerging role for BAG3 in gynaecological malignancies. Br J Cancer (2021). https://doi.org/10.1038/s41416-021-01446-2

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