Evaluation of copper chaperone ATOX1 as prognostic biomarker in breast cancer

Abstract

Copper is involved in different hallmarks of cancer, including metastasis, but responsible copper-binding proteins and pathways are not clear. The copper chaperone ATOX1 was recently shown to play a role in breast cancer cell migration, which is a key step in metastasis. Since most cancer-related deaths are due to metastasis, we hypothesized that ATOX1 mRNA expression may be associated with breast cancer disease progression and thus, a prognostic biomarker in breast cancer. We therefore studied the association of ATOX1 expression levels with clinicopathological parameters and survival for 1904 breast cancer patients using the METABRIC data set. Our results indicate ATOX1 expression levels as a potential prognostic biomarker for ER-positive subtypes and early stages of breast cancer. Pre-clinical studies and clinical trials are desired to identify the molecular roles of ATOX1 in these conditions.

The Multifaceted Roles of Copper in Cancer: A Trace Metal Element with Dysregulated Metabolism, but Also a Target or a Bullet for Therapy

“…Atox1 may be a potential prognostic biomarker for estrogen-receptor (ER)-positive and early stages of breast cancers because increased expression levels of Atox1 correlated with poor survival for stages 1 and 2 breast cancers. However, preclinical studies and clinical trials are required to better understand the carcinogenic role of Atox1 [128]. In melanoma, a correlation between the overexpression of Atox1 and poor prognosis was observed because the knockdown of Atox1 decreased cell growth and BRAF V600E-dependent signaling in human melanoma cell lines [58].…”

The Multifaceted Roles of Copper in Cancer: a Trace Metal Element with Dysregulated Metabolism, but also a Target or a Bullet for Therapy

“…Atox1 may be a potential prognostic biomarker for estrogen-receptor (ER)-positive and early stages of breast cancers, since increased expression levels of Atox1 correlated with poor survival for stages 1 and 2 breast cancers. However, preclinical studies and clinical trials are required to better understand the carcinogenic role of Atox1 [49]. In melanoma, a correlation between overexpression of Atox1 and poor prognosis was observed, since the knockdown of Atox1 decreased cell growth and BRAF V600E-dependent signaling in human melanoma cell lines [47].…”

Cu Homeostasis in Bacteria: The Ins and Outs

“…Remarkably, many of the proteins involved in bacterial Cu homeostasis have eukaryotic homologues that are closely associated with different metabolic disorders, including Menkes and Wilson disease [ 353 ]. In addition, targeting Cu metabolism has emerged in recent years as a novel strategy in cancer treatment, and several growth factors, transcription regulators and signaling molecules were shown to respond to cellular Cu availability [ 354 , 355 , 356 , 357 , 358 ]. Thus, understanding the general and conserved principles of Cu handling in both prokaryotic and eukaryotic cells undoubtedly continues to provide uncharted avenues for developing novel treatment regimens for human diseases.…”