A Comparative Review of Pregnancy and Cancer and Their Association with Endoplasmic Reticulum Aminopeptidase 1 and 2

Abstract

The fundamental basis of pregnancy and cancer is to determine the fate of the survival or the death of humanity. However, the development of fetuses and tumors share many similarities and differences, making them two sides of the same coin. This review presents an overview of the similarities and differences between pregnancy and cancer. In addition, we will also discuss the critical roles that Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and 2 may play in the immune system, cell migration, and angiogenesis, all of which are essential for fetal and tumor development. Even though the comprehensive understanding of ERAP2 lags that of ERAP1 due to the lack of an animal model, recent studies have shown that both enzymes are associated with an increased risk of several diseases, including pregnancy disorder pre-eclampsia (PE), recurrent miscarriages, and cancer. The exact mechanisms in both pregnancy and cancer need to be elucidated. Therefore, a deeper understanding of ERAP’s role in diseases can make it a potential therapeutic target for pregnancy complications and cancer and offer greater insight into its impact on the immune system.

Shedding Light on the Role of ERAP1 in Axial Spondyloarthritis

“…It also plays a role in the proteolytic cleavage of cytokine receptors, such as tumor necrosis factor receptor 1 (TNFR1), IL6R2, and IL1R2, which are expressed on the cell surface via receptor cleavage. The shedding of cell surface receptors by ERAP1 can control the cellular immune response by modulating receptor availability on the cell surface, which causes a reduction in proinflammatory signaling [37].…”

“…The risk of developing AS is as high as 5% to 7% in HLA-B27-positive individuals. The genetic association of the aminopeptidase polymorphisms ERAP1 and ERAP2 with axSpA is the second strongest after HLA-B27, accounting for 15% to 25% of the population risk [37]. The genetic interaction between ERAP1 and HLA-B27 in axSpA indicates that peptide cleavage and presentation contribute to axSpA susceptibility [66].…”

“…The genetic interaction between ERAP1 and HLA-B27 in axSpA indicates that peptide cleavage and presentation contribute to axSpA susceptibility [66]. Together, HLA-B27 and ERAP explain 70% of the genetic risk of developing SpA [37]. The bulk of ERAP1 SNPs associated with SpA are located close to the catalytic site (aa residues 346 and 349), in the binding groove (aa residues 725 and 730), or close to locations that potentially affect conformational rearrangements (aa residues 528 and 575).…”

Placental Related Disorders of Pregnancy 2.0

“…The first two systematic reviews investigate pregnancy latency biomarkers after preterm premature rupture of membranes [ 2 ] and atypical pre-eclampsia before 20 weeks of gestation [ 3 ]. This is followed by detailed reviews of the apelinergic system in pregnancy [ 4 ]; serum screen markers for trisomy 21 and the crucial involvement of the placenta [ 5 ]; how the placenta can provide a protective role in SARS-CoV-2 transplacental transmission [ 6 ]; endoplasmic reticulum aminopeptidase 1 and 2 and their involvement in pregnancy and cancer [ 7 ]; and how rodent and rabbit models can be used in pre-eclampsia research [ 8 ]. Moreover, this Special Issue also contains original articles with novel data covering hypothyroidism [ 9 ] and pre-eclampsia/fetal growth restriction [ 10 , 11 , 12 , 13 ].…”