WBP2 and its network of transcription coregulators in an expanding repertoire of human cancers.

Abstract

Dysregulation of transcription coregulators is common in cancers, supporting the key role for this group of proteins in cancer development. WW domain-binding protein 2 (WBP2) transcription coactivator is an emerging oncogene, first discovered in breast cancer and increasingly implicated in other human cancers except sex-related cancers. Here, we review the latest findings on the roles of WBP2 in human cancers and explore its function and network of transcriptional coregulators in ovarian and prostate cancers. Through the creation of a protein-interaction map of the sex hormone receptor coregulators, biologically meaningful observations and testable hypotheses were generated. Coupling the protein-interaction map with information from published literature reveals that the WBP2 transcription coactivator might play a role in ovarian and prostate cancers via protein complexes comprising Hippo pathway signaling components YAP and TAZ, Wnt pathway-related β-Catenin, and sex hormone receptor coregulators such as CBP/P300, NCOA3, and PGC-1α. Meta-analysis of public databases also revealed aberrant levels of these proteins in ovarian and prostate cancer, and found WBP2 overexpression in the immunoreactive ovarian cancer subtype, further supporting the role of these specific protein complexes in ovarian cancer. Finally, we reviewed the challenges in chemo and hormonal therapy and posit that WBP2-positive ovarian and prostate cancer might benefit from combinational therapy involving hormonal and immunotherapy.