Involvement of the PRL-PAK1 Pathway in Cancer Cell Migration.

Abstract

Prolactin (PRL) is a polypeptide hormone synthesized in the lactotrophs of the adenohypophysis and in extrahypophyseal glands (such as the prostate and breasts) where it promotes their development. PRL is also involved in cancer development in these glands. It has been shown to stimulate cancer cell migration, suggesting its possible involvement in metastasis, in which cell migration plays an essential role. However, the role of PRL in cell migration is still unclear. Moreover, the intracellular mechanisms activated by PRL to carry out cell migration are less well understood. PRL exerts its effects via the PRL receptor (PRLR), which leads intracellularly to phosphorylation of Janus protein kinase 2 (JAK2), which in turn phosphorylates p21-activated protein kinase (PAK1), leading to an increase in cell migration. Although several studies have described the involvement of the PRL-PAK1 pathway in breast cancer cell migration, the molecular mechanisms have not been fully elucidated and there is no integration of these into signaling pathways. This study was conducted based on literature search of review articles and original research in the PubMed database, using the following keywords: PRL, cell migration, PRL and cell migration, PAK1 and signaling pathways. The aim of this review article was to describe the major signaling pathways controlled by PRL-PAK1 and propose a comprehensive model of the signaling pathways associated with PRL-PAK1.