Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?

Abstract

Cancer is a heterogeneous disease, and even tumors with similar clinicopathological characteristics show different biology, behavior, and treatment responses. As a result, there is an urgent need to define new prognostic and predictive markers to make treatment options more personalized. According to the latest findings, nucleobindin-2/nesfatin-1 (NUCB2/NESF-1) is an important factor in cancer development and progression. Nucleobindin-2 is a precursor protein of nesfatin-1. As NUCB2 and nesfatin-1 are colocalized in each tissue, their expression is often analyzed together as NUCB2. The metabolic function of NUCB2/NESF-1 is related to food intake, glucose metabolism, and the regulation of immune, cardiovascular and endocrine systems. Recently, it has been demonstrated that high expression of NUCB2/NESF-1 is associated with poor outcomes and promotes cell proliferation, migration, and invasion in, e.g., breast, colon, prostate, endometrial, thyroid, bladder cancers, or glioblastoma. Interestingly, nesfatin-1 is also considered an inhibitor of the proliferation of human adrenocortical carcinoma and ovarian epithelial carcinoma cells. These conflicting results make NUCB2/NESF-1 an interesting target of study in the context of cancer progression. The present review is the first to describe NUCB2/NESF-1 as a new prognostic and predictive marker in cancers.

Expression of NUCB2/NESF-1 in Breast Cancer Cells

“…Accumulating evidence indicates that NUCB2/NESF-1 is a new cancer-related protein. Recent studies have shown that NUCB2 is overexpressed in breast, bladder, prostate, clear renal cell carcinoma, ovarian, thyroid, endometrial, gastric, and colon cancer cells compared to that in normal tissue [ 4 ].…”

“…NUCB2/NESF1 was first identified in the KM3 acute lymphoblastic leukemia cell line as the EF-hand family of calcium-binding protein in the 1990s [ 4 ]. In 2006, Oh et al identified nesfatin-1 (NESF-1) in the hypothalamic nuclei, an 82-amino-acid peptide derived from the cleavage of nucleobindin-2 [ 5 ].…”

Application of solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) and comparison of both detection techniques (DAD and FLD) to analyse nesfatin-1 in fetal bovine serum samples

“…Nucleobindin-2 (NUCB2) is a precursor protein of nesfatin-1 (NESF-1). Since NUCB2 and NESF-1 are colocalized in each tissue, their expression is often analysed together as NUCB2 [6]. The metabolic function of NUCB2/NESF-1 is related to food intake, glucose metabolism, and the immunoregulation/ the immune, cardiovascular and endocrine systems [6][7][8][9][10].…”

Premetazoan Origin of Neuropeptide Signaling

“…NUCB precursors contain a signal peptide, dibasic cleavage sites, and leucine zipper and EF-hand motifs. It has been shown that these precursors can act as calcium and DNA-binding proteins in addition to producing mature neuropeptides ( Miura et al 1992 , 1994 ; Kmiecik et al 2021 ). NUCB precursors encode three different potential peptides, known as nesfatin-1, 2, and 3.…”