Int J Stem Cells.  2021 May;14(2):168-179. 10.15283/ijsc20121.

The Role of Nkx3.1 in Cancers and Stemness

• Antao AM
• Ramakrishna S
• Kim KS

• KMID: 2515993
• DOI: http://doi.org/10.15283/ijsc20121

Abstract

The well-known androgen-regulated homeobox gene, NKX3.1, is located on the short arm of chromosome 8. It is the first known prostate epithelium-specific marker, and is a transcription factor involved in development of the testes and prostate. In addition to specifying the prostate epithelium and maintaining normal prostate secretory function, Nkx3.1 is an established marker for prostate cancer. Over the years, however, this gene has been implicated in various other cancers, and technological advances have allowed determination of its role in other cellular functions. Nkx3.1 has also been recently identified as a factor capable of replacing Oct4 in cellular reprogramming. This review highlights the role of this tumor suppressor and briefly describes its functions, ranging from prostate development to maintenance of stemness and cellular reprogramming.

Keyword

Cellular reprogramming; CARNs; Prostate development; Prostate cancer

Figure

• 

  Fig. 1 Structural features of the homeobox protein Nkx3.1. (A) Nkx3.1 is a 234 amino acid protein that contains three major structural motifs crucial for its interactions with other proteins and DNA. Amino acids 1-123 correspond to the N terminal region and are depicted in purple. The homeodomain region corresponds to amino acids 124-183 and contains three helices, Helix I depicted in blue, Helix II in green and Helix III in yellow. The C terminal region corresponds to amino acids 184-234, depicted in brown. (B) Nkx3.1 protein structure. The structural feature of Nkx3.1 protein have been identified by nuclear magnetic resonance spectroscopy (22, 23). The N terminal is depicted in purple, Helix I in blue, Helix II in green, Helix III in yellow and the C terminal in brown.

• 

  Fig. 2 The activities of Nkx3.1. (A) The role of Nkx3.1 in the IL-6-STAT3 signalling pathway during iPSC in-duction. Nkx3.1 is a target of STAT3, downstream of IL6r activation and is essential during reprogramming. IL-6r deficiency during reprogramming is reported to be rescued by Nkx3.1 alone or in cooperation with STAT3. However, knockdown of STAT3 decreases Nkx3.1 protein level, whereas knockdown of Nkx3.1 blocks iPSC reprogramming (86). (B) Nkx3.1 can replace Oct4 in cellular reprogramming, and promotes the generation of iPSCs with a similar efficiency to Oct4.

Reference

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