The PI3K/Akt Pathway: Emerging Roles in Skin Homeostasis and a Group of Non-Malignant Skin Disorders

Abstract

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway regulates cell proliferation, differentiation, and migration, along with angiogenesis and metabolism. Additionally, it could mediate skin development and homeostasis. There is much evidence to suggest that dysregulation of PI3K/Akt pathway is frequently associated with several human cutaneous malignancies like malignant melanoma (MM), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (SCC), as well as their poor outcomes. Nevertheless, emerging roles of PI3K/Akt pathway cascade in a group of common non-malignant skin disorders including acne and psoriasis, among others, have been recognized. The enhanced understanding of dysfunction of PI3K/Akt pathway in patients with these non-malignant disorders has offered a solid foundation for the progress of updated therapeutic targets. This article reviews the latest advances in the roles of PI3K/Akt pathway and their targets in the skin homeostasis and progression of a wide range of non-malignant skin disorders and describes the current progress in preclinical and clinical researches on the involvement of PI3K/Akt pathway targeted therapies.

Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes

“…Inactivation of PI3K/AKT signaling provides a novel approach in psoriasis management [61]. The classical PI3K/AKT pathway leads to activation of intracellular signaling that regulates cell metabolism, growth, proliferation, differentiation and migration [18,43,62]. Among malignant skin disorders, dysregulation of PI3K/AKT pathway is also associated with acne and psoriasis.…”

“…The Th1/Th2/Th17 imbalance activates PI3K/AKT/mTOR pathway and results in the occurrence and development of psoriasis. The PI3K binds to AKT and thereby in turn activates the mTOR, which promotes keratinocyte hyperproliferation and inhibits differentiation [18]. Inactivation of PI3K and AKT pathways reduced proliferative effects in psoriatic keratinocytes and improved psoriasis-like pathologies in vitro and in vivo [14,60,63].…”

“…In addition, the activated psoriatic keratinocytes respond with deranged proliferation and differentiation programs [6,[11][12][13][14]. Signaling pathways, known to be implicated in psoriasis development, are the Janus kinase/signal transducer and activator of transcription (JAK/STAT), the nuclear factor kappa B (NF-κB) and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway [1,5,[15][16][17][18].…”

The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review

“…These findings sugnified that iMSCs-exosome could stimulate the skin cells growth by inducing ERK1/2 possibly as a result of activating the EGFR-Ras-Raf axis [ 105 ]. Irrespective of ERK axes, ligand binding to EGFR can support autophosphorylation and resultant activation of both PI3K/AKT and STAT3 pathways, which in turn, stimulate skin cell proliferation as well as survival [ 106 , 107 ].…”

Long Noncoding RNA H19: A Novel Therapeutic Target Emerging in Oncology Via Regulating Oncogenic Signaling Pathways

“…Increasing evidence has shown the emerging roles of the phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway in cell proliferation, differentiation, migration, angiogenesis, apoptosis, and other physiological activities ( Teng et al, 2021 ). Under abnormal conditions, this signaling pathway can be overactivated, and PI3K can activate its downstream factor serine/threonine kinase Akt to regulate gene expression.…”