Endocrine-Disrupting Chemicals’ (EDCs) Effects on Tumour Microenvironment and Cancer Progression: Emerging Contribution of RACK1

We provide an analysis of immunomodulatory and cancer-promoting effects of different Endocrine disruptors in shaping tumour microenvironment, with a final focus on the scaffold protein Receptor for Activated C Kinase 1 as a pivotal molecular player due to its dual role in immune and cancer contexts

Erica Buoso; Mirco Masi; Marco Racchi; Emanuela Corsini

2020

Scholarcy highlights

  • Steroid hormones can interact with specific receptors, orchestrating a vast set of physiological functions, including growth, development, reproduction, energy imbalance, metabolism, immunity and behaviour
  • Since Receptor for Activated C Kinase 1 is a relevant Endocrine disruptors target that responds to steroid-active compounds, it could be considered a molecular bridge between the endocrine-regulated tumour microenvironment and the innate immune system
  • We provide an analysis of immunomodulatory and cancer-promoting effects of different EDCs in shaping tumour microenvironment, with a final focus on the scaffold protein RACK1 as a pivotal molecular player due to its dual role in immune and cancer contexts
  • P,p’-DDE exerts a stronger repression effect than p’p’-DDT, according to its higher affinity for AR. These results demonstrate that RACK1 is a bridge between the endocrine system and the innate immune and it can be regulated in an opposite way by agonists and antagonists of AR, supporting RACK1 as a target of EDCs
  • The identification of RACK1 as a possible EDC target in the immune context and, at the same time, its importance in tumour progression may indicate that RACK1 could play a dual role in BC- and prostate cancer-associated Tumour Microenvironment establishment and in modification of the immune response, related to xeno-oestrogenic EDCs
  • Since alterations of RACK1 expression in both in BC and PC cells have been reported to be mediated by NF-κB through PI3K/Akt signalling cascade, oestrogenic EDCs can mediate G protein-coupled oestrogen receptor activation leading to RACK1 overexpression, promoting the acquisition of RACK1 extra-ribosomal functions which, in turn, favours Epithelial-Mesenchymal transition
  • Since alterations of Receptor for Activated C Kinase 1 expression in both in BC and prostate cancer cells have been reported to be mediated by NF-κB through PI3K/Akt signalling cascade, oestrogenic Endocrine disruptors can mediate G protein-coupled oestrogen receptor activation leading to RACK1 overexpression, promoting the acquisition of RACK1 extra-ribosomal functions which, in turn, favours Epithelial-Mesenchymal transition

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