Hippo signaling in epithelial stem cells

Abstract

Over the past decade, discoveries on Hippo signaling have revealed a complex signaling network integrating various signaling pathways to modulate tissue homeostasis, organ size control, tissue repair, and regeneration. Malfunction of the Hippo pathway is associated with tumor and cancer development. Moreover, Hippo signaling has been proposed to act in numerous stem cells in a variety of organisms. Recently, more attention has been paid to define the functions of the Hippo pathway in tissue-specific stem cells, which have great potential to be used in cell-based therapies. Here we provide an overview of its roles in regulating stem cells in epithelial tissues and its potential implications in related cancers.

Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy

“…Recently, several studies have indicated that Hippo-mediated YAP1 phosphorylation is really a fundamental input for YAP1 regulation, but not the only one. Inflammation, DNA damage, and ROS or mechanical signals can represent separate signals with partly independent pathways that can regulate YAP1 phosphorylation and activity 2526272829…”

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO

“…Especially during pregnancy and within 3 years after birth, the composition of the microorganisms in the intestinal microbiome is affected by the delivery method of the infant as well as differences in diet composition 26. Antibiotic use during infancy induces changes in the composition of the intestinal microbial strain, and this is associated with suppressed T helper 1 (Th1)-type immunity after normal birth as well as progressively increased serum IgE levels and regulatory T cells, which are known to suppress T helper 2 (Th2)-type immune responses 2728…”

Roles of the Hippo pathway in lung development and tumorigenesis

“…1) have not been studied in lung cancer, it will be more interesting to test whether these Hippo components are also involved in lung development and tumorigenesis. Moreover, since the Hippo pathway plays important roles in the formation of cancer stem cells such as breast cancer stem cells 16,90,94,95 and lung cancer stem cells play critical roles in lung tumorigenesis and therapy, [96][97][98] it will be very important to examine whether and how the Hippo pathway is involved in lung cancer stem cell development. 18,20,[89][90][91][92] Therefore, a new direction to explore is how the Hippo pathway is involved in the response of lung cancers to current chemotherapy (e.g., Taxol, cisplatin, etc) or target therapy [e.g., EGFR inhibitors (erlotinib, gefitinib, etc)] and whether the Hippo components can be used as prognostic or diagnostic biomarkers for drug resistance in lung cancer therapy.…”

“…In addition, since the Hippo pathway has been shown to interact with many other pathways such as the Wnt pathway, which is critical for lung homeostasis, 93 it will be very interesting to further explore how the Hippo interacts with these known Hippo-interacting signaling pathways or identify novel signaling pathways interacting with the Hippo signaling in regulating lung development, tumorigenesis and metastasis. Moreover, since the Hippo pathway plays important roles in the formation of cancer stem cells such as breast cancer stem cells 16,90,94,95 and lung cancer stem cells play critical roles in lung tumorigenesis and therapy, [96][97][98] it will be very important to examine whether and how the Hippo pathway is involved in lung cancer stem cell development. Most recently, a transcriptome meta-analysis of lung cancer reveals that high numbers of Hippo pathway component (NF2, LATS1, PTPN14, YAP1, TAZ, TAOK and FAT1) gene fusions were observed in lung cancer and are independent prognostic factors for poor survival in lung cancer.…”