NES

What is NES?

Intermediate filament protein family is an important structural system of cytoskeleton. Nestin (NES) is a class VI protein of intermediate filament protein family.

Nestin, is a connexin that participates in the composition of the cytoskeleton. Nestin was first found to be expressed in neural stem cells and as an important marker of neural stem / progenitor cells. In recent years, it has been found that it is also expressed in many cancers.

The Structure of NES

The mouse nestin gene is located in the F1 region of chromosome 3, which is 6143 bp in length and contains three introns and four exons.

The nestin consists of three parts: the head (N - terminal), the rod domain and the tail (C - terminal).

The rod domain is a super-helical structure composed of 310 amino acids. The amino acid sequence of this region has 16%-29% homology with the other five types of intermediate filament proteins that have been found.

Nestin has a longer C-terminal (479 amino acids) and a shorter N-terminal (only 11 amino acids). Both C-terminal and N-terminal are non-helical structures.

The particularity of nestin protein structure determines that nestin can not be self-assembled and must be assembled into heterodimers with other intermediate filament proteins (vimentin, α-internexin, etc.).

The Expression of NES

Nestin was first found to be specifically expressed in neural stem cells, and is often used as a marker of neural progenitor cells.

Subsequent studies found that nestin is not limited to neural stem cells, but also expressed in vascular endothelial progenitor cells, embryonic pancreas, lung and other tissues.

In addition, nestin and desmin are co-expressed in the developing heart. Nestin was expressed in hair follicles, islets, testis and other tissues during development.

Studies have shown that when tissue injury occurs, the number of nestin + cells in the tissue injury site will significantly increase.

In addition to being expressed in normal tissues, nestin is also expressed in a variety of tumors, including central nervous system tumors, pancreatic cancer, gastrointestinal stromal tumors, prostate cancer, breast cancer, malignant melanoma and thyroid tumors.

The Function of NES

As an important component of the cytoskeleton, the main function of intermediate filament protein may be to protect cell homeostasis as a highly alienated stress protein in a variety of stress environments.

Nestin interacts with cellular receptor molecules and participates in the control of cell polarization, migration and invasion.

By reacting with integrin, nestin promotes neutrophil chemotaxis during inflammation.

Nestin is closely related to embryonic development.

Nestin+ cells play an important role in tissue damage repair and homeostasis maintenance. In normal tissue, the number of Nestin+ cells is very small, when tissue injury occurs, the number of nestin+ cells in the injured part of the tissue will increase significantly.

Nestin may be involved in the self-renewal and maintenance of MSCs.

Studies have found that nestin is also expressed in a variety of tumor tissues, and the expression of nestin is positively correlated with tumor proliferation and metastasis. Therefore, nestin is also considered as a marker of many kinds of tumor stem cells.

Latest Research Progress

Abnormal antioxidant capacity of tumors is considered as a potential mechanism of malignant tumor. Regulation of oxidative stress is emerging as an anticancer therapy.

A recent studies shows that nestin knockout cells were found to be more sensitive to oxidative stress in non-small cell lung cancer (NSCLC). The studies have shown that Nestin regulates redox homeostasis in lung cancer cells through Keap1-Nrf2 feedback loops. Nestin-Keap1-Nrf2 axis endows NSCLC with oxidative stress resistance.

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