Two decades of a protooncogene HPIP/PBXIP1: Uncovering the tale from germ cell to cancer

Hematopoietic PBX interacting protein (HPIP or pre-B-cell leukemia transcription factor interacting protein (PBXIP1) was discovered two decades ago as a corepressor of pre-B-cell leukemia homeobox (PBX) 1 with a vital functional role in hematopoiesis. Later it emerged as a potential biomarker of poor prognosis and tumorigenesis for more than a dozen different cancers. It regulates aggressive cancer phenotypes, cell proliferation, metastasis, EMT, etc. The anomaly in the regulation of HPIP is linked with physiological disorders like renal fibrosis, chronic kidney disease and osteoarthritis. Scientists have unraveled more than twenty interacting proteins of HPIP and its functional role in various physiological and cellular processes that involves normal neuronal development, embryogenesis, endometrium decidualization, and germ cell proliferation. Over the past 20 years, we have witnessed the emerging role of HPIP and its association with a myriad of cellular activities ranging from germ cell proliferation to cancer aggressiveness, modulating multitude of signaling cascades like TGF-β1, PI3K/AKT, Wnt, mTOR, and Sonic hedgehog signaling pathways. This review will give the current understanding of HPIP, in terms of its diverse functions, theoretical ideas, and further explore cellular links and promising areas that need to be investigated. We also provide a comprehensive overview of the transcript variants of HPIP and distinct sets of transcription factors regulating their expression, which may help to understand the role of HPIP in various cellular or physiological conditions.