Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma

Abstract

Most malignant mesotheliomas (MPMs) frequently show activated forms of Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which transcriptionally regulates the receptor for hyaluronic acid-mediated motility (RHAMM). As RHAMM is involved in cell migration and invasion in various tumors, we speculated that hyaluronic acid (HA) in pleural fluid might affect the progression of mesothelioma by stimulating cell migration and invasion through RHAMM. The level of RHAMM expression was decreased by YAP1/TAZ knockdown, and conversely increased by forced expression of the active form of YAP1, suggesting that RHAMM was regulated by YAP1/TAZ in MPM cells. Cell migration and invasion were also decreased by YAP1/TAZ or RHAMM knockdown. Notably, HA treatment increased cell motility and invasion, and this was abolished by RHAMM knockdown, suggesting that HA may augment local progression of MPM cells via RHAMM. Furthermore, treatment with fluvastatin, which regulates RHAMM transcription by modulating YAP1/TAZ activity, decreased the motility and invasion of MPM cells. Collectively, these data suggest that HA is an “unfavorable” factor because it promotes malignancy in mesothelioma and that the YAP1/TAZ-RHAMM axis may have potential value as a therapeutic target for inhibition of disease progression in MPM.

Amphiregulin contributes to airway remodeling in chronic allograft dysfunction after lung transplantation

“…[24][25][26][27] Moreover, prior studies have implicated HA in promoting mesenchymal progenitor cell migration and enhancing invasive cell properties. 28,29 Although our study points to the airway epithelium as the most abundant cell type contributing to Areg expression in the context of OB, we also observed Areg expression in many infiltrating inflammatory cells. Current data suggest that Areg can be expressed by multiple populations of activated immune cells and can also influence immune cell function.…”

“…Such modification of the HA matrix has been demonstrated to promote leukocyte adhesion, thus contributing to local immune activation, and is known to enhance matrix stiffness, which can further amplify ECM synthesis by lung fibroblasts . Moreover, prior studies have implicated HA in promoting mesenchymal progenitor cell migration and enhancing invasive cell properties …”

Adhesive Hemostatic Conducting Injectable Composite Hydrogels with Sustained Drug Release and Photothermal Antibacterial Activity to Promote Full‐Thickness Skin Regeneration During Wound Healing

“…Hyaluronic acid (HA), as a natural polysaccharide produced by fibroblasts in the wound repair stages of proliferation, can mediate cellular signaling, promote cell migration, and induce morphogenesis and matrix organization, which enhances the repair process of soft tissue wound . Besides, HA has good biocompatibility, biodegradability, moisture retention, and gelation property, which favors the design of injectable hydrogel dressing.…”

<b>Clinicopathological and prognostic significance of nuclear UGDH localization in lung adenocar</b><b>cinoma</b>

“…Nuclear expression levels were higher in LC-2/ad cells than in A549 cells, consistent with the results of IHC. ties (29). UGDH expression is one of the factors that controls the production of glycosaminoglycans as important components of ECM (5).…”