NRBP2, or Nuclear Receptor Binding Protein 2, is a pseudokinase. It has been implicated in multiple biological processes, especially in the regulation of tumor progression and cell survival. It is associated with pathways such as the 5'-adenosine monophosphate (AMP)-activated protein kinase/ mammalian target of rapamycin (AMPK/mTOR) and Akt signaling pathways, which are crucial for cell metabolism, growth, and survival [1,2]. Its role in neural progenitor differentiation and cell survival also highlights its importance in normal development [3].

In cancer research, NRBP2 has shown tumor-suppressive effects. In breast cancer, its downregulation in tumor tissues correlated with poor prognosis. Overexpression of NRBP2 in breast cancer cells suppressed cell proliferation, invasion, and epithelial-to-mesenchymal transition (EMT) both in vitro and in an orthotopic breast tumor model in nude mice, and this was related to the regulation of the AMPK/mTOR pathway [1]. In hepatocellular carcinoma, NRBP2 was downregulated in CD133+ cancer stem cells. Overexpression increased chemosensitivity, restrained cell stemness, and regulated the Akt signaling pathway [2]. In medulloblastoma, NRBP2 was downregulated, and its overexpression decreased cell numbers, increased cell death, and impaired cell migration and invasion in vitro [5]. In thyroid carcinoma, overexpression of NRBP2 suppressed cell growth, reduced the expression of tumor microenvironment (TME) markers, M2 macrophage polarization, and angiogenesis, and GATA1 negatively regulated NRBP2 by recruiting histone deacetylase2 (HDAC2) to its promoter [4].

In conclusion, NRBP2 functions as a tumor suppressor in multiple cancer types, influencing processes like cell proliferation, invasion, EMT, and chemosensitivity. Its association with key signaling pathways provides insights into potential therapeutic strategies. The studies using in vivo models such as nude mice and in vitro cell-based experiments have been instrumental in uncovering these functions, contributing to our understanding of cancer biology and potential treatment targets.