Yes-associated protein-1 overexpression in ocular surface squamous neoplasia; a potential diagnostic marker and therapeutic target

Julius, Peter; Siyumbwa, Stepfanie N.; Maate, Fred; Moonga, Phyllis; Kang, Guobin; Kaile, Trevor; West, John T.; Wood, Charles; Angeletti, Peter C.

doi:10.3389/fonc.2023.1213426

Cited by 4 publications

(3 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High YAP1 expression was correlated with nuclear and cytoplasmic localization (hereinafter referred to as YAP1 high), while low YAP1 expression was correlated with cytoplasmic localization (hereafter referred to as YAP1 low). These findings are consistent with those of the previous report ( 20 , 21 ).…”

Section: Resultssupporting

confidence: 94%

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: Resultssupporting

confidence: 94%

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

“…These conjunctival and corneal cellular responses in horses with OSSN likely reflect inflammation associated with immune responses to the malignant cells. For example, previous histological studies of equine OSSN have demonstrated an inflammatory cell infiltrate in most of the tumor biopsies that were examined, indicative of an ongoing anti-tumor immune response [59,60]. In addition to the plethora of immune pathways, cilium assembly was downregulated in OSSN eyes, which is in line with previous reports of dysregulation in ocular diseases [61].…”

Section: Discussionsupporting

confidence: 85%

Impact of Equine Ocular Surface Squamous Neoplasia on Interactions between Ocular Transcriptome and Microbiome

Chow,

Flaherty,

Pezzanite

et al. 2024

Veterinary Sciences

View full text Add to dashboard Cite

Ocular surface squamous neoplasia (OSSN) represents the most common conjunctival tumor in horses and frequently results in vision loss and surgical removal of the affected globe. Multiple etiologic factors have been identified as contributing to OSSN progression, including solar radiation exposure, genetic mutations, and a lack of periocular pigmentation. Response to conventional treatments has been highly variable, though our recent work indicates that these tumors are highly responsive to local immunotherapy. In the present study, we extended our investigation of OSSN in horses to better understand how the ocular transcriptome responds to the presence of the tumor and how the ocular surface microbiome may also be altered by the presence of cancer. Therefore, we collected swabs from the ventral conjunctival fornix from 22 eyes in this study (11 with cytologically or histologically confirmed OSSN and 11 healthy eyes from the same horses) and performed RNA sequencing and 16S microbial sequencing using the same samples. Microbial 16s DNA sequencing and bulk RNA sequencing were both conducted using an Illumina-based platform. In eyes with OSSN, we observed significantly upregulated expression of genes and pathways associated with inflammation, particularly interferon. Microbial diversity was significantly reduced in conjunctival swabs from horses with OSSN. We also performed interactome analysis and found that three bacterial taxa (Actinobacillus, Helcococcus and Parvimona) had significant correlations with more than 100 upregulated genes in samples from animals with OSSN. These findings highlight the inflammatory nature of OSSN in horses and provide important new insights into how the host ocular surface interacts with certain microbial populations. These findings suggest new strategies for the management of OSSN in horses, which may entail immunotherapy in combination with ocular surface probiotics or prebiotics to help normalize ocular cell and microbe interactions.

show abstract

“…During our previous investigation, exploring the potential associations between oncogenic viruses and ocular surface squamous neoplasia (OSSN) (Julius et al, 2021;Julius et al, 2022;Julius et al, 2023), we encountered a patient with ocular KS among our cohort of 458 patients recruited with ocular surface tumors at the University Teaching Hospitals (UTH) Eye Hospital in Lusaka, Zambia. As an incidental finding, the ocular surface KS tumor analysis revealed the co-infection and co-localization of KSHV and EBV.…”

Section: Introductionmentioning

confidence: 99%

Co-infection and co-localization of Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus in HIV-associated Kaposi sarcoma: a case report

Julius,

Kang,

Siyumbwa

et al. 2023

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

Kaposi sarcoma (KS), a multifocal vascular neoplasm frequently observed in HIV-positive individuals, primarily affects the skin, mucous membranes, visceral organs, and lymph nodes. KS is associated primarily with Kaposi sarcoma-associated herpesvirus (KSHV) infection. In this case report, we present a rare occurrence of co-infection and co-localization of KSHV and Epstein-Barr virus (EBV) in KS arising from the conjunctiva, which, to our knowledge, has not been reported previously. Immunohistochemistry (IHC), DNA polymerase chain reaction (PCR), and EBV-encoded RNA in situ hybridization (EBER-ISH) were utilized to demonstrate the presence of KSHV and EBV infection in the ocular KS lesion. Nearly all KSHV-positive cells displayed co-infection with EBV. In addition, the KS lesion revealed co-localization of KSHV Latency-Associated Nuclear Antigen (LANA) and EBV Epstein Barr virus Nuclear Antigen-1 (EBNA1) by multi-colored immunofluorescence staining with different anti-EBNA1 antibodies, indicating the possibility of interactions between these two gamma herpesviruses within the same lesion. Additional study is needed to determine whether EBV co-infection in KS is a common or an opportunistic event that might contribute to KS development and progression.

show abstract

Yes-associated protein-1 overexpression in ocular surface squamous neoplasia; a potential diagnostic marker and therapeutic target

Cited by 4 publications

References 82 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

Impact of Equine Ocular Surface Squamous Neoplasia on Interactions between Ocular Transcriptome and Microbiome

Co-infection and co-localization of Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus in HIV-associated Kaposi sarcoma: a case report

Contact Info

Product

Resources

About