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

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1219
Author(s):  
Yan Teng ◽  
Yibin Fan ◽  
Jingwen Ma ◽  
Wei Lu ◽  
Na Liu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Akt Pathway ◽  
Skin Disorders ◽  
Phosphatidylinositol 3 Kinase ◽  
Skin Development ◽  
Wide Range ◽  
Malignant Skin ◽  
Solid Foundation ◽  
And Migration ◽  
Poor Outcomes

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.

scholarly journals The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 857 ◽  
Author(s):  
Manel Hammouda ◽  
Amy Ford ◽  
Yuan Liu ◽  
Jennifer Zhang
Keyword(s):  
Cell Carcinoma ◽  
Skin Disorders ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Cellular Processes ◽  
Downstream Effector ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Common Skin ◽  
Apoptosis And Inflammation

The c-Jun N-terminal kinases (JNKs), with its members JNK1, JNK2, and JNK3, is a subfamily of (MAPK) mitogen-activated protein kinases. JNK signaling regulates a wide range of cellular processes, including cell proliferation, differentiation, survival, apoptosis, and inflammation. Dysregulation of JNK pathway is associated with a wide range of immune disorders and cancer. Our objective is to provide a review of JNK proteins and their upstream regulators and downstream effector molecules in common skin disorders, including psoriasis, dermal fibrosis, scleroderma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.

OSI-906 Restores The Sensitivity of Ovarian Clear Cell Carcinoma To Cisplatin By Targeting The IGF1R/AKT Pathway

2021 ◽  
Author(s):  
Li Liu ◽  
Changyan Liang ◽  
Chenya Zhuo ◽  
Huiyun Jiang ◽  
Huixia Ye ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Animal Experiments ◽  
Akt Pathway ◽  
Ovarian Clear Cell Carcinoma ◽  
Pathway Activation ◽  
And Migration

Abstract Among the various histologic subtypes of ovarian cancers (OCs), ovarian clear cell carcinoma (OCCC) represents a great challenge due to its disease aggressiveness and resistance to chemotherapy. IGF1 is overexpressed in epithelial ovarian cancer (EOC), and IGF1 pathway activation is related to the chemoresistance of various cancers. In this study, we found that the expression level of IGF1 was higher in OCCC than in the most common type of OC, high-grade serous adenocarcinoma (HGSC). Then, we investigated the role of IGF1 pathway activation in the progression of OCCC, observing that activation of the IGF1 pathway using IGF1 promoted the proliferation and migration of ES2 cells, while inactivation of the IGF1 pathway using the selective IGF1R inhibitor OSI-906 reversed the alteration mediated by IGF1. Based on the role of the IGF1 pathway in cancer chemoresistance, we proposed that OSI-906 may restore the sensitivity of OCCC to cisplatin. We first validated that IGF1 increased the IC50 value of cisplatin in ES2 cells, while OSI-906 decreased it. Then we confirmed that IGF1 decreased the apoptosis rate of ES2 cells induced by cisplatin, while OSI-906 increased it. Finally, we conducted animal experiments to investigate whether OSI-906 helps cisplatin control the growth of OCCC. As expected, OSI-906 increased the effect of cisplatin in attenuating the growth of OCCC in vivo. Therefore, we conclude that using OSI-906 may be an effective method to restore the sensitivity of OCCC to cisplatin by targeting the IGF1R/AKT pathway.

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