Zinc’s Association with the CmPn/CmP Signaling Network in Breast Cancer Tumorigenesis

Abstract

It is well-known that serum and cellular concentrations of zinc are altered in breast cancer patients. Specifically, there are notable zinc hyper-aggregates in breast tumor cells when compared to normal mammary epithelial cells. However, the mechanisms responsible for zinc accumulation and the consequences of zinc dysregulation are poorly understood. In this review, we detailed cellular zinc regulation/dysregulation under the influence of varying levels of sex steroids and breast cancer tumorigenesis to try to better understand the intricate relationship between these factors based on our current understanding of the CmPn/CmP signaling network. We also made some efforts to propose a relationship between zinc signaling and the CmPn/CmP signaling network.

Key Members of the CmPn as Biomarkers Distinguish Histological and Immune Subtypes of Hepatic Cancers

“…Pathways functional enrichment results obtained from significantly altered genes in HCC clinical samples demonstrated perturbation to key cancer signaling pathways including cell cycle, DNA replication, spliceosomes/lysosomes, pancreatic cancer signaling pathways, and pancreatic secretion pathways ( Figure 2 (C-2)). Interestingly, we also observed dysregulation in hormone signaling pathways including oocyte meiosis and PRG-mediated oocyte maturation ( Figure 2 (C-2)), which were also altered pathways observed in all of our breast cancer studies [ 16 , 17 , 23 , 27 , 28 ]. Functional enrichment results obtained from significantly altered genes in CCA clinical samples demonstrated perturbation to key cancer signaling pathways including cell population proliferation/differentiation, cell junction assembly, Wnt signaling, PI3K-Akt, and Notch signaling ( Figure 2 (D-2)), which were also observed to be dysregulated in all of our breast cancer studies [ 16 , 17 , 23 , 27 , 28 ].…”

“…Interestingly, we also observed dysregulation in hormone signaling pathways including oocyte meiosis and PRG-mediated oocyte maturation ( Figure 2 (C-2)), which were also altered pathways observed in all of our breast cancer studies [ 16 , 17 , 23 , 27 , 28 ]. Functional enrichment results obtained from significantly altered genes in CCA clinical samples demonstrated perturbation to key cancer signaling pathways including cell population proliferation/differentiation, cell junction assembly, Wnt signaling, PI3K-Akt, and Notch signaling ( Figure 2 (D-2)), which were also observed to be dysregulated in all of our breast cancer studies [ 16 , 17 , 23 , 27 , 28 ]. We also observed newly dysregulated pathways, not observed in our breast cancer studies, including disruption of ECM–receptor interactions, complement/coagulation cascades, PPAR pathways, bile secretion, peroxisomes, sterol/cholesterol homeostasis, and ABC transporters ( Figure 2 (D-2)), which are known to influence liver tumorigenesis.…”

“…Shared down-regulated pathways in C1 subtype, for both HCCs and CCAs, included fatty acid degradation and lipid/lipoprotein metabolism ( Supplementary Figures S1C and S2C ). To our surprise, Wnt signaling was observed to be up regulated only in HCCs ( Supplementary Figures S1C ), which was also a main altered pathway observed in our previous breast cancer studies investigating effects of altered CmPn expression [ 16 , 17 , 23 , 27 , 28 ].…”

“…Recent studies have highlighted the crucial role of the CmPn signaling network in the development of multiple types of cancer [ 16 , 17 , 22 , 23 , 26 , 27 , 28 ]. It has been demonstrated that the mPRs and nPRs play equally important roles in PRG signaling and that organs that metabolize PRG are susceptible to changes in CmPn members’ expression during tumorigenesis [ 12 ].…”

“…The CSC, which is comprised of KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3), has been observed to interact with mPRs and nPRs to form the CSC-mPR-PRG-nPR (CmPn) signaling network under PRG actions [ 19 , 20 , 21 , 22 ]. This network is involved in angiogenesis and tumorigenesis of multiple types of cancers, including liver and breast cancers [ 16 , 17 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”