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Review
. 2021 May 26;22(11):5687.
doi: 10.3390/ijms22115687.

The Multifaceted Nature of Nucleobindin-2 in Carcinogenesis

Anna Skorupska  1 , Rafał Lenda  1 , Andrzej Ożyhar  1 , Dominika Bystranowska  1
Affiliations
Review

The Multifaceted Nature of Nucleobindin-2 in Carcinogenesis

Anna Skorupska et al. Int J Mol Sci. .

Abstract

Nucb2 is a multifunctional protein associated with a variety of biological processes. Multiple studies have revealed that Nucb2, and its derivative nesfatin-1, are involved in carcinogenesis. Interestingly, the role of Nucb2/nesfatin-1 in tumorigenesis seems to be dual-both pro-metastatic and anti-metastatic. The implication of Nucb2/nesfatin-1 in carcinogenesis seems to be tissue dependent. Herein, we review the role of Nucb2/nesfatin-1 in both carcinogenesis and the apoptosis process, and we also highlight the multifaceted nature of Nucb2/nesfatin-1.

Keywords: Nucb2; apoptosis; biomarker; carcinogenesis; nesfatin-1; tumors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The dual role of Nucb2/nesfatin-1 in carcinogenesis. (A) The pro-metastatic function of Nucb2/nesfatin-1. (B) The involvement of Nucb2/nesfatin-1 in apoptosis processes. Nucb2 mediates metastasis through the LKB1/AMPK/mTORC1/ZEB1 pathways. Nucb2 is thought to participate in the adaptation of cancer cells to ERm stress, which also promotes cell metastasis. On the other hand, Nucb2/nesfatin-1 is implicated in the apoptosis process through such pathways as the mTOR/RhoA/ROCK and JNK-1/2/p38MAPK pathways. Apoptosis induction by Nucb2/nesfatin-1 is also exerted by the regulation of apoptotic gene expression, e.g., Bax and Bcl-2. Additionally, Nucb2 is a substrate of caspase cleavage, which also indicates the participation of Nucb2 in apoptosis.
Figure 2
Figure 2
Scheme of proposed Nucb2 mediated signaling pathways in colon cancer and LUAD. Nucb2 enhances migration, invasion, and mesenchymal phenotype in colon cancer through the LKB1/AMPK/TORC1/ZEB1 pathways. Nucb2 also plays an oncogenic role in LUAD by increasing the expression of N-cadherin and vimentin and promoting the deficiency of the E-cadherin level. See the text for more details.
Figure 3
Figure 3
Scheme of proposed Nucb2-induced apoptosis in ovarian cancer and in adrenocortical carcinoma. Nucb2 exerts apoptosis in ovarian epithelial cell carcinoma through the mTOR/RhoA/ROCK pathways. Nucb2 also alters the phosphorylation pattern of kinases belonging to the family of serine/threonine mitogen-activated protein kinases (MAPKs), resulting in elevated levels of phosphorylated p-JNK-1/2, and p-p38MAPK, and decreased levels of phosphorylated p-ERK1/2. See the text for more details.
Figure 4
Figure 4
Schematic representation of major Nucb2-protein interactions important in the regulation of the tumorigenesis process. (A) Nucb2–necdin interaction disrupts the secretion of Nucb2 and leads to the accumulation of Nucb2 in the cytoplasm. (B) Ca2+-dependent Nucb2–ARTS-1 interaction leads to the release of both the full-length and truncated forms of TNFR1. (C) Suppression of the Nucb2–Gαi3 interaction occurs due to the Ca2+-dependent conformational change of Nucb2’s structure. See the text for more details.
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