Mammalian sterile 20‑like kinase 1 expression and its prognostic significance in patients with breast cancer

Lin, Xinhua; Cai, Fengfeng; Wang, Ming‐Hong; Pan, Xin; Wang, Fang; Cai, Lei; Cui, Rongrong; Su, Chen; Biskup, Ewelina

doi:10.3892/ol.2017.6852

Cited by 14 publications

(14 citation statements)

References 41 publications

(49 reference statements)

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“…In colorectal cancer, loss of cytoplasmic MST1 has been associated with higher T and/or N stage, higher tumor grade and poor prognosis [35]. Similarly, MST1 has been reported to be downregulated in breast cancer and proposed as a strong prognostic and predictive for disease-free survival [36,37]. Although we did not find a correlation between cytoplasmic expression and clinicopathological features, the nuclear expression of MST1 was significantly associated with pT stage and progression in our GBC cohort.…”

Section: Discussioncontrasting

confidence: 48%

“…In our study, the immunohistochemical evaluation of MST1 expression confirmed a diminished expression in GBC compared with CC. The anticancer effects of MST1 have been reported for numerous types of cancer, including colorectal [34,35], breast [10,36,37] and lung cancers [38]. It should be noted that cytoplasmic expression of MST1 in cancer cells has been related with its function as a protective molecule acting in the canonical Hippo signaling pathway, through the inhibition of oncogenic YAP/TAZ [33].…”

Section: Discussionmentioning

confidence: 99%

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Hippo-YAP1 Is a Prognosis Marker and Potentially Targetable Pathway in Advanced Gallbladder Cancer

García

Rosa

Vargas

et al. 2020

Cancers

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Gallbladder cancer is an aggressive disease with late diagnosis and no efficacious treatment. The Hippo-Yes-associated protein 1 (YAP1) signaling pathway has emerged as a target for the development of new therapeutic interventions in cancers. However, the role of the Hippo-targeted therapy has not been addressed in advanced gallbladder cancer (GBC). This study aimed to evaluate the expression of the major Hippo pathway components mammalian Ste20-like protein kinase 1 (MST1), YAP1 and transcriptional coactivator with PDZ-binding motif (TAZ) and examined the effects of Verteporfin (VP), a small molecular inhibitor of YAP1-TEA domain transcription factor (TEAD) protein interaction, in metastatic GBC cell lines and patient-derived organoids (PDOs). Immunohistochemical analysis revealed that advanced GBC patients had high nuclear expression of YAP1. High nuclear expression of YAP1 was associated with poor survival in GBC patients with subserosal invasion (pT2). Additionally, advanced GBC cases showed reduced expression of MST1 compared to chronic cholecystitis. Both VP treatment and YAP1 siRNA inhibited the migration ability in GBC cell lines. Interestingly, gemcitabine resistant PDOs with high nuclear expression of YAP1 were sensitive to VP treatment. Taken together, our results suggest that key components of the Hippo-YAP1 signaling pathway are dysregulated in advanced gallbladder cancer and reveal that the inhibition YAP1 may be a candidate for targeted therapy.

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Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Hippo-YAP1 Is a Prognosis Marker and Potentially Targetable Pathway in Advanced Gallbladder Cancer

García

Rosa

Vargas

et al. 2020

Cancers

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“… 41 protein 110 0.027 0.03 low 10% of SEP as cutoff breast cancer Lin X-Y et al . 42 protein 98 0.010 0.002 low detection on plasma by ELISA, average as cutoff colorectal cancer Yu J et al . 43 mRNA 46 0.0008 NA low microarray, ROC curve to set the cutoff colorectal cancer Minoo P et al .…”

Section: Resultsmentioning

confidence: 99%

Hippo pathway affects survival of cancer patients: extensive analysis of TCGA data and review of literature

Poma

Torregrossa

Bruno

et al. 2018

Sci Rep

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The disruption of the Hippo pathway occurs in many cancer types and is associated with cancer progression. Herein, we investigated the impact of 32 Hippo genes on overall survival (OS) of cancer patients, by both analysing data from The Cancer Genome Atlas (TCGA) and reviewing the related literature. mRNA and protein expression data of all solid tumors except pure sarcomas were downloaded from TCGA database. Thirty-two Hippo genes were considered; for each gene, patients were dichotomized based on median expression value. Survival analyses were performed to identify independent predictors, taking into account the main clinical-pathological features affecting OS. Finally, independent predictors were correlated with YAP1 oncoprotein expression. At least one of the Hippo genes is an independent prognostic factor in 12 out of 13 considered tumor datasets. mRNA levels of the independent predictors coherently correlate with YAP1 in glioma, kidney renal clear cell, head and neck, and bladder cancer. Moreover, literature data revealed the association between YAP1 levels and OS in gastric, colorectal, hepatocellular, pancreatic, and lung cancer. Herein, we identified cancers in which Hippo pathway affects OS; these cancers should be candidates for YAP1 inhibitors development and testing.

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“…Kinase signaling is a powerful and central cellular mechanism that mediates signal transduction events and is involved in a wide range of nearly all cellular processes including, but not limited to, the control of cell cycle progression, transcriptional regulation, cell transformation, proliferation, differentiation, and apoptosis. Given its central role in cellular function, aberrant regulation of kinase signaling can profoundly affect homeostasis and has been found to be involved in many disease states including insulin resistance [ 3 , 4 ], autoimmunity [ 5 , 6 ], viral infection [ 7 , 8 ], and oncogenesis [ 9 , 10 ]. Hence, assessing the kinome can provide insight into complex pathological processes across a wide array of diseases and has also been a well-studied target for therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Methods and approaches to disease mechanisms using systems kinomics

Berard

Kroeker

McQueen

et al. 2018

Synthetic and Systems Biotechnology

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All cellular functions, ranging from regular cell maintenance and homeostasis, specialized functions specific to cellular types, or generating responses due to external stimulus, are mediated by proteins within the cell. Regulation of these proteins allows the cell to alter its behavior under different circumstances. A major mechanism of protein regulation is utilizing protein kinases and phosphatases; enzymes that catalyze the transfer of phosphates between substrates [1]. Proteins involved in phosphate signaling are well studied and include kinases and phosphatases that catalyze opposing reactions regulating both structure and function of the cell. Kinomics is the study of kinases, phosphatases and their targets, and has been used to study the functional changes in numerous diseases and infectious diseases with aims to delineate the cellular functions affected. Identifying the phosphate signaling pathways changed by certain diseases or infections can lead to novel therapeutic targets. However, a daunting 518 putative protein kinase genes have been identified [2], indicating that this protein family is very large and complex. Identifying which enzymes are specific to a particular disease can be a laborious task. In this review, we will provide information on large-scale systems biology methodologies that allow global screening of the kinome to more efficiently identify which kinase pathways are pertinent for further study.

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Mammalian sterile 20‑like kinase 1 expression and its prognostic significance in patients with breast cancer

Cited by 14 publications

References 41 publications

Hippo-YAP1 Is a Prognosis Marker and Potentially Targetable Pathway in Advanced Gallbladder Cancer

Hippo-YAP1 Is a Prognosis Marker and Potentially Targetable Pathway in Advanced Gallbladder Cancer

Hippo pathway affects survival of cancer patients: extensive analysis of TCGA data and review of literature

Methods and approaches to disease mechanisms using systems kinomics

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