Hippo‐YAP signaling activation and cross‐talk with PI3K in oral cancer: A retrospective cohort study

Rodrigo, Juan P.; Rodríguez-Santamarta, Tanía; Corte, Daniela; García-de-la-Fuente, Vanessa; Rodríguez-Torres, Nerea; Lequerica-Fernández, Paloma; Lorz, Corina; García-Pedrero, Juana M.; Rodríguez, J.C. De Vicente

doi:10.1111/odi.14350

Cited by 3 publications

(2 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, high YAP1 expression was associated with worse prognosis. Collectively, these results are somewhat consistent with those of a previous report ( 8 , 34 , 35 ) and suggest that YAP1 is involved in oncogenesis and aggressiveness involving EMT in OSCC. EMT is a complex and reversible biological process, in which an epithelial tumor changes its polar, adhesive phenotype to a mesenchymal phenotype characterized by an increase in cell migration and invasion potential, cytoskeleton remodeling, and resistance to apoptosis ( 22 ).…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

The significance of Hippo pathway protein expression in oral squamous cell carcinoma

Amano,

Matsubara,

Kihara

et al. 2024

Front. Med.

View full text Add to dashboard Cite

IntroductionThe Hippo pathway consists of mammalian sterile 20-like kinase 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and yes-associated protein (YAP)1. Herein, we present the first report on the significance of major Hippo pathway protein expression in oral squamous cell carcinoma (OSCC).MethodsThe analyses included oral epithelial dysplasia (OED, n = 7), carcinoma in situ (CIS, n = 14), and oral squamous cell carcinoma (OSCC, n = 109).ResultsCytoplasmic expression of MST1, LATS1, and LATS2 was low in OED, CIS, and OSCC. The cytoplasmic expression of MST2 was high in OED (5/7 cases), CIS (9/14 cases), and poorly differentiated OSCC (8/8 cases) but was low/lost in a proportion of differentiated OSCC (60/101 cases). The expression of YAP1 was associated with differentiation; low YAP expression was significantly more frequent in well-differentiated OSCC (35/71 cases), compared to moderately and poorly differentiated OSCC (11/38 cases). An infiltrative invasion pattern was associated with a high expression of MST2 and high expression of YAP1. The high expression of YAP1 was associated with features of epithelial-to-mesenchymal transition (EMT), such as the loss of E-cadherin and high expression of vimentin, laminin 5, and Slug. High expression of protein arginine methyltransferase (PRMT) 1 or 5, which positively regulates YAP activity, was associated with the high expression of YAP1 (p < 0.0001).ConclusionAmong the major Hippo pathway proteins, MST2 displayed a distinctive expression pattern in a significant proportion of differentiated OSCC, suggesting a possible differential role for MST2 depending on the course of OSCC progression. A high YAP1 expression may indicate aggressive OSCC with EMT via PRMTs at the invasive front.

show abstract

Section: Discussionsupporting

confidence: 92%

“…Furthermore, YAP1 has been shown to drive cancer metastasis ( 6 ). In OSCC, the Hippo pathway plays an essential role in disease progression and YAP1 activation, both of which correlate with unfavorable prognosis ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

The significance of Hippo pathway protein expression in oral squamous cell carcinoma

Amano,

Matsubara,

Kihara

et al. 2024

Front. Med.

View full text Add to dashboard Cite

show abstract

The Hippo pathway in oral diseases and treatments: A review

2024

Medicine

View full text Add to dashboard Cite

This review aims to provide a recent update on the Hippo pathway in oral diseases. The Hippo pathway plays a crucial role in organ development, tissue regeneration, wound healing, maintaining epithelial homeostasis, and modulating the immune system. Globally, billions of people suffer from various oral diseases, posing significant public health risks and resulting in substantial economic losses. This article reviews the recent advancements in the research on the Hippo signaling pathway and its effectors in various conditions related to oral health. The implications of Hippo signaling in various dental fields, including endodontics, orthodontics, periodontology, oral implantology, oral and maxillofacial surgery, and oncology are discussed. It provides readers with an overview of the regulatory role of the Hippo pathway in the development of various oral diseases and the potential for exploiting this pathway for developing targeted therapeutics.

show abstract

Tumor-Intrinsic Perinuclear LOXL2: Prognostic Relevance and Relationship with YAP1 Activation Status in Oral Squamous Cell Carcinoma

Rodrigo,

Moreno-Bueno,

Lequerica-Fernández

et al. 2024

Pathobiology

View full text Add to dashboard Cite

Introduction: Lysyl oxidase-like 2 (LOXL2) expression and function is frequently altered in different cancers but scarcely explored in oral squamous cell carcinoma (OSCC). This prompted us to investigate the clinical relevance of LOXL2 expression pattern in OSCC and also a possible crosstalk with Hippo/YAP1 pathway signaling. Methods: Immunohistochemical analysis of LOXL2 protein expression was performed in 158 OSCC patient samples, together with Yes-associated protein 1 (YAP1) activation status. Correlations with clinicopathological parameters and patient survival were assessed. Results: Tumor cell-intrinsic LOXL2 expression showed two distinct expression patterns: diffuse cytoplasmic staining (64.6%) and heterogeneous perinuclear staining (35.4%). Remarkably, perinuclear LOXL2 staining was significantly associated with lymph node metastasis, advanced clinical stage and perineural invasion. Moreover, patients harboring tumors with perinuclear LOXL2 expression exhibited significantly poorer disease-specific survival (DSS) rates, and perinuclear LOXL2 positivity gradually increased in relation to YAP1 activation. Patients harboring tumors with concomitant perinuclear LOXL2 and fully active YAP1 exhibited the worst DSS. Multivariate Cox analysis further revealed combined perinuclear LOXL2 and fully active YAP1 as a significant independent predictor of poor DSS. Conclusion: Tumor-intrinsic perinuclear LOXL2 emerges as a clinically and biologically relevant feature associated with advanced disease, tumor aggressiveness, and poor prognosis in OSCC. Moreover, this study unprecedentedly uncovers a functional relationship between perinuclear LOXL2 and YAP1 activation with major prognostic implications. Notably, combined perinuclear LOXL2 and fully active YAP1 was revealed as independent predictor of poor prognosis. These findings encourage targeting oncogenic LOXL2 functions for personalized treatment regimens.

show abstract

Hippo‐YAP signaling activation and cross‐talk with PI3K in oral cancer: A retrospective cohort study

Cited by 3 publications

References 46 publications

The significance of Hippo pathway protein expression in oral squamous cell carcinoma

The significance of Hippo pathway protein expression in oral squamous cell carcinoma

The Hippo pathway in oral diseases and treatments: A review

Tumor-Intrinsic Perinuclear LOXL2: Prognostic Relevance and Relationship with YAP1 Activation Status in Oral Squamous Cell Carcinoma

Contact Info

Product

Resources

About