Comprehensive Analysis of the Expression of Key Genes Related to Hippo Signaling and Their Prognosis Impact in Ovarian Cancer

Kubelac, Paul; Braicu, Cornelia; Ráduly, Lajos; Chiroi, Paul; Nuțu, Andreea; Cojocneanu, Roxana; Budişan, Liviuţa; Berindan‐Neagoe, Ioana; Achimaș-Cădariu, Patriciu

doi:10.3390/diagnostics11020344

Cited by 4 publications

(4 citation statements)

References 51 publications

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“…Our results suggest that loss of LATS1/2 in HGSOC could be a marker of an aggressive disease, or a distinct clinical phenotype. Currently, there are only three studies addressing the relationship of LATS1 and LATS2 levels and clinical outcomes in ovarian cancer, and they reported contradicting findings [53, 56, 57]. Of note, studies have suggested that LATS2 may even act as an oncogene in some cancers, by showing that low expression of LATS2 correlated with better patient outcome [58, 59].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of LATS Kinases in Ovarian Cancer Activates Cyclin D1/CDK4 and Decreases DYRK1A Activity

Sesay

Saini

Pajimola

et al. 2022

Preprint

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The controlled division of cells requires a coordination of multiple cellular pathways. Hippo pathway controls the organ size and restricts cell proliferation in response to the signals from cell surface receptors, and genetic alterations in the components of this pathway are common in cancer. LATS1 and LATS2 are homologous protein kinases that relay the signals from the environment to the Hippo effector YAP by direct phosphorylation that promotes its degradation. The genes encoding these kinases undergo frequent genetic losses in human cancers, with particularly high rates in high grade serous ovarian carcinoma (HGSOC), a highly lethal cancer with poorly understood mechanisms of pathogenesis and progression. We hypothesized that loss of LATS kinases could be a driver in this cancer and investigated signaling pathways downstream of LATS that could influence the ovarian cancer tumorigenic phenotypes. Depletion of both LATS1 and LATS2 was required to increase cell proliferation and disrupt the assembly of the cell-cycle regulatory DREAM complex. LATS-depleted human ovarian cancer cells formed bigger tumors in the immunocompromised mice, consistent with their tumor suppressor role. DREAM assembly depends on the activity of DYRK1A protein kinase, which was decreased in the LATS1/2-depleted cells. Furthermore, loss of LATS kinases increased the inhibitory phosphorylation of the retinoblastoma (Rb) family proteins, further promoting the DREAM disassembly that was rescued by CDK4 inhibitor palbociclib. Our study describes a crosstalk between the Hippo pathway and the cell cycle regulatory machinery converging on cyclin D1, a major regulator of the Rb tumor suppressor family, and highlights cellular pathways that could contribute to ovarian cancer pathogenesis and progression.

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Section: Discussionmentioning

confidence: 99%

Inhibition of LATS Kinases in Ovarian Cancer Activates Cyclin D1/CDK4 and Decreases DYRK1A Activity

Sesay

Saini

Pajimola

et al. 2022

Preprint

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“…Quantitative data from a total of 592 melanoma samples (S), including metastatic melanoma (MM) (DFCI, Nature Medicine 2019; n=144) and skin cutaneous melanoma (SCM) (TCGA, Pan-Cancer Atlas; n=448), were evaluated by using cBioPortal for Cancer Genomics (https://www.cbioportal.org/) in the study. The GEO2R analysis tool provided by The National Center for Biotechnology Information (NCBI) was used to evaluate data sets [GSE65904 (10,11), GSE22155 (12), and GSE120878 (13)] from GEO database to determine whether WWC1 was associated with melanoma carcinogenesis and progression.…”

Section: Datasets Used For Gene-based Identification and Analysis Of ...mentioning

confidence: 99%

“…GSE65904, GSE22155, and GSE120878 datasets were found suitable for the study. The raw file formats of GSE65904, GSE22155, and GSE120878 datasets were downloaded (10)(11)(12)(13). The expression data were analyzed using GraphPad Prism 8.…”

Section: Analysis Of Expression Datamentioning

confidence: 99%

“…The Hippo signaling pathway is an effective regulator of cell proliferation and differentiation (10). Dysregulation of the Hippo pathway can cause tumorigenesis (11,12). The mammalian Hippo pathway includes two major effectors containing WW domain such as Yes Associated Protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (13).…”

Section: Introductionmentioning

confidence: 99%

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In silico Evaluation of WWC1 in Melanoma Using Bioinformatic Analyses

Çolak¹,

Ünal²,

Bolkent³

2022

ejb

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Objective: It is suggested that WWC1 has an active role in melanoma progression. Therefore, it was aimed to evaluate the WWC1 gene expression profiles in melanoma, an aggressive malignant skin tumor. Materials and Methods:Quantitative data from melanoma samples (n=592) were clinically evaluated using cBioPortal. Gene expression (GSE65904 and GSE22155) and gene methylation datasets (GSE120878) were retrieved from the Gene Expression Omnibus (GEO) database. Using the GeneMANIA database, the functions of given genes and pathways were evaluated. The STRING database achieved a protein-protein interaction (PPI) network was used to visualize it.Results: Mutations in the WWC1 were found in 6.7% of all melanoma samples, 8% of skin cutaneous melanoma, and 2.8% of metastatic melanoma. When the GeneMANIA platform was used to analyze gene interactions, it was determined that the WWC1 gene shared common protein domains with three genes, was co-expressed with five genes, and interacted with 17 other genes. According to the function analysis results, the most effective of the ten functions of WWC1 was Hippo signaling, with a coverage value of 0.16 (p=0.009). In addition, it then played a role in Notch signaling and organ growth. When the protein-protein interactions were examined, it was determined that it interacted with ten proteins and was co-expressed with nine. Conclusion:The findings demonstrated the potential of WWC1 to be effective in the progression of melanoma. Further research is needed to provide a more accurate analysis of WWC1 expression and methylation.

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Discovery and preliminary validation of a new panel of personalized ovarian cancer biomarkers for individualized detection of recurrence

Ren,

Prassas,

Soosaipillai

et al. 2023

F1000Res

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Background: Following first-line treatment, over 80% of advanced ovarian cancer cases suffer recurrence. Treatment of patients with recurrence based on CA125 has not resulted in improvements in outcome postulating that we need biomarkers for earlier detection. A tumor-specific array of serum proteins with advanced proteomic methods could identify personalized marker signatures that detect relapse at a point where early intervention may improve outcome. Methods: For our discovery phase, we employed the proximity extension assay (PEA) to simultaneously measure 1,104 proteins in 120 longitudinal serum samples (30 ovarian cancer patients). For our validation phase, we used PEAs to concurrently measure 644 proteins (including 21 previously identified candidates, plus CA125 and HE4) in 234 independent, longitudinal serum samples (39 ovarian cancer patients). Results: We discovered 23 candidate personalized markers (plus CA125 and HE4), in which personalized combinations were informative of recurrence in 92% of patients. In our validation study, 21 candidates were each informative of recurrence in 3-35% of patients. Patient-centric analysis of 644 proteins generated a refined panel of 33 personalized tumor markers (included 18 validated candidates). The panel offered 91% sensitivity for identifying individualized marker combinations that were informative of recurrence. Conclusion: Tracking individualized combinations of tumor markers may offer high sensitivity for detecting recurrence early and aid in prompt clinical referral to imaging and treatment interventions.

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Comprehensive Analysis of the Expression of Key Genes Related to Hippo Signaling and Their Prognosis Impact in Ovarian Cancer

Cited by 4 publications

References 51 publications

Inhibition of LATS Kinases in Ovarian Cancer Activates Cyclin D1/CDK4 and Decreases DYRK1A Activity

Inhibition of LATS Kinases in Ovarian Cancer Activates Cyclin D1/CDK4 and Decreases DYRK1A Activity

In silico Evaluation of WWC1 in Melanoma Using Bioinformatic Analyses

Discovery and preliminary validation of a new panel of personalized ovarian cancer biomarkers for individualized detection of recurrence

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