NDRGs in Breast Cancer: A Review and In Silico Analysis

Authors

Emilly S Villodre
Anh P N Nguyen
Bisrat G Debeb

Publication Date

3-29-2024

Journal

Cancers

Abstract

Simple Summary

Breast cancer is the most common cancer in women and one of the deadliest. While survival rates for patients with breast cancer have seen notable improvements in recent decades, current treatment strategies still face significant limitations, especially for patients with aggressive, therapy-resistant, and metastatic breast cancers. For this reason, it is important to identify new targets in order to develop more effective therapeutic strategies. The N-myc downstream regulated gene family (NDRGs), comprising NDRG1, NDRG2, NDRG3, and NDRG4, has been previously described as tumor suppressors. However, recent findings challenge this perception, particularly for NDRG1, which has demonstrated a critical role in driving tumor growth and metastasis in aggressive forms of breast cancer. In this review, we discuss the role of the NDRG family members in breast cancer, which is supported by analyses of genomic and transcriptomic data from various independent breast cancer patient cohorts.

Abstract

The N-myc downstream regulated gene family (NDRGs) includes four members: NDRG1, NDRG2, NDRG3, and NDRG4. These members exhibit 53–65% amino acid identity. The role of NDRGs in tumor growth and metastasis appears to be tumor- and context-dependent. While many studies have reported that these family members have tumor suppressive roles, recent studies have demonstrated that NDRGs, particularly NDRG1 and NDRG2, function as oncogenes, promoting tumor growth and metastasis. Additionally, NDRGs are involved in regulating different signaling pathways and exhibit diverse cellular functions in breast cancers. In this review, we comprehensively outline the oncogenic and tumor suppressor roles of the NDRG family members in breast cancer, examining evidence from in vitro and in vivo breast cancer models as well as tumor tissues from breast cancer patients. We also present analyses of publicly available genomic and transcriptomic data from multiple independent cohorts of breast cancer patients.

Keywords

breast cancer, NDRGs, NDRG1, NDRG family, tumor promoter, tumor suppressor

Comments

PMID: 38611020