BTB protein family and human breast cancer: signaling pathways and clinical progress

Abstract

Background: Breast cancer is considered the number one killer of women both in China and abroad, and the leading cause of cancer death. It severely affects female health-related quality of life. Broad-complex, tramtrack, bric à brac (BTB) protein family was first discovered in drosophila as early as in 1993 by Godt D and peers, since then, more family members and their critical biological functions were uncovered. Moreover, researchers around the world have recently demonstrated that numerous signaling pathways connect BTB family members and human breast cancer.

Purpose: In this review, we critically discuss these findings regarding the essential mechanisms and functions of the BTB protein family in mediating the organic processes of human breast cancer. Meanwhile, we summarize the signaling pathways the BTB protein family participates in. And we address that BTB proteins regulate the growth, apoptosis, and other behaviors of breast cancer cells. We also point out the future directions for further studies in this field.

Methods: The relevant online literatures have been reviewed for this article.

Conclusion: This review could offer an update on novel molecular targets for treating human breast cancer and new insights into BTB protein family research.

Keywords: BTB protein; Breast cancer; Signaling pathways.

Fig. 1

Breast cancer-related BTB proteins and their architectures

Fig. 2

Regulators, targets, mechanisms, and functions of BTB protein in breast cancer. Specific proteins, RNAs, and lipopolysaccharides are essential upstream regulators in mediating various signaling pathways and are intimately associated with the BTB protein family. Afterward, several anti-tumor and pro-tumor biological functions ensue, which mediate the development, differentiation, tumorigenesis, and other biological properties of breast cancer (Created with BioRender.com)

Fig. 3

Signaling pathways BTB protein involved in breast cancer. Through communications with several small molecular targets, promotive or inhibitive signals were carried into the cell, which activate specific signaling pathways and exercise relevant biological functions through a cascade of reactions

Fig. 4

Using Kaplan–Meier Plotter (https://kmplot.com/analysis/) to analyze the clinical role of BTB protein in breast cancer, the clinical index was set as “RFS”. BTB protein family members, which are significantly associated with the prognostics of breast cancer patients, were illustrated here. KCTD10 and ZBTB33 are suggested to be tumor activators. BTBD7, RhoBTB2, SPOP, ZBTB4, ZBTB16, ZBTB7A, and PATZ1 are suggested to be tumor suppressors. No significant impact of other BTB proteins was detected

Fig. 5

Using the UALCAN database (http://ualcan.path.uab.edu/) to analyze the expression of BTB proteins in breast cancer. BTB proteins that possess significant roles in the prognostics were listed, while other proteins were omitted; ***P < 0.001 vs. adjacent normal tissue; **P < 0.01 vs. adjacent normal tissue; *P < 0.05 vs. adjacent normal tissue

Fig. 6

Mode of the function of CUL3