Pathological significance and prognostic role of LATS2 in prostate cancer

Matsuda, Tsuyoshi; Miyata, Yasuyoshi; Nakamura, Yuichiro; Otsubo, Asato; Mukae, Yuta; Harada, Junki; Mitsunari, Kensuke; Matsuo, Tomohiro; Ohba, Kenkichi; Furusato, Bungo; Sakai, Hideki

doi:10.1002/pros.24226

Cited by 4 publications

(2 citation statements)

References 46 publications

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“…Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration, and plays a critical role in genomic stability (33). Moreover, a recent study has demonstrated that LATS2 is a potential therapeutic target as a predictor for outcome in patients with PC (34). DDX3X is a member of the large DEAD-box protein family and functions as a tumor suppressor.…”

Section: Comparative Analysis Of Genomic Profiles In Tumor Samplesmentioning

confidence: 99%

Precision medicine targets for prostate cancers in African American men

jung

2024

Preprint

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To investigate molecular mechanisms underlying prostate cancer health disparities, the primary prostate epithelial cell cultures were established from the tumors and adjacent non-tumor tissues of prostatectomy specimens of African American (AA) men surgically treated for cancer. We performed whole genome sequencing of 10 tumor samples paired with 10 non-tumor controls derived from the same donors using next generation sequencing technologies. Here, we report that tumor cells harbor various mutations with insertion/deletion variants, some of which are unique in individual specimens. Comparative analyses of genomic profiling revealed that 40% of the cohort harbored more than 20 mutated genes with high impactful consequences, coinciding with clinical-pathological characteristics of patients, including higher Gleason’s grade and T3 clinical stage. Several mutated genes were oncogenes or potentially oncogenic variants of tumor suppressors, affecting key pathways in the carcinogenic process. Our study highlights unique somatic gene alterations in AA patient-derived prostate tumor cells offering potentially targetable drivers in support of precision medicine for individual prostate cancers rather than disease specific therapies.

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Section: Comparative Analysis Of Genomic Profiles In Tumor Samplesmentioning

confidence: 99%

Precision medicine targets for prostate cancers in African American men

jung

2024

Preprint

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“…PDE5 inhibitors restore nitric oxide (Kalsi et al, 2005;Lee et al, 2022) and are selective vasodilators of the NO-cGMP signaling pathway (Aversa et al, 2019;Ahmed et al, 2021). PDE5 inhibitors have been shown to benefit vasculature oxygenation (Morelli et al, 2011;Michel et al, 2015), prevent ischemia-hypoxia (Saito et al, 2014;Zarifpour et al, 2015;Fujii et al, 2019), and reduce microvascular/endothelial dysfunction (Cellek et al, 2014;Ölmestig et al, 2020;Statsenko and Urologiia, 2021); they also reduce oxidative stress (Matsuo et al, 2020), inflammation (Vignozzi et al, 2013;Peixoto and Gomes, 2015), amyloids (Kang et al, 2022), and prostate weight (Kobayashi et al, 2022).…”

Section: Nitric Oxide Bioavailability and Expression Signalingmentioning

confidence: 99%

Understanding human aging and the fundamental cell signaling link in age-related diseases: the middle-aging hypovascularity hypoxia hypothesis

Phua

2023

Front. Aging

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Aging-related hypoxia, oxidative stress, and inflammation pathophysiology are closely associated with human age-related carcinogenesis and chronic diseases. However, the connection between hypoxia and hormonal cell signaling pathways is unclear, but such human age-related comorbid diseases do coincide with the middle-aging period of declining sex hormonal signaling. This scoping review evaluates the relevant interdisciplinary evidence to assess the systems biology of function, regulation, and homeostasis in order to discern and decipher the etiology of the connection between hypoxia and hormonal signaling in human age-related comorbid diseases. The hypothesis charts the accumulating evidence to support the development of a hypoxic milieu and oxidative stress-inflammation pathophysiology in middle-aged individuals, as well as the induction of amyloidosis, autophagy, and epithelial-to-mesenchymal transition in aging-related degeneration. Taken together, this new approach and strategy can provide the clarity of concepts and patterns to determine the causes of declining vascularity hemodynamics (blood flow) and physiological oxygenation perfusion (oxygen bioavailability) in relation to oxygen homeostasis and vascularity that cause hypoxia (hypovascularity hypoxia). The middle-aging hypovascularity hypoxia hypothesis could provide the mechanistic interface connecting the endocrine, nitric oxide, and oxygen homeostasis signaling that is closely linked to the progressive conditions of degenerative hypertrophy, atrophy, fibrosis, and neoplasm. An in-depth understanding of these intrinsic biological processes of the developing middle-aged hypoxia could provide potential new strategies for time-dependent therapies in maintaining healthspan for healthy lifestyle aging, medical cost savings, and health system sustainability.

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Pathological significance and prognostic role of LATS2 in prostate cancer

et al. 2021

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Background Large tumor suppressor 2 (LATS2) is an important regulator of the Hippo pathway and it plays crucial roles in cell survival and behaviors. Herein, we evaluated the pathological roles of LATS2 in prostate cancer (PC), for which very little information is available. Methods Cell proliferation, migration, and invasion in response to the siRNA‐mediated knockdown (KD) LATS2 expression were evaluated in two PC cell lines (LNCaP and PC3). The expression of LATS2 in specimens from 204 PC patients was investigated immunohistochemically, and the relationships between its expression and clinicopathological features, proliferation index (PI; measured using an anti‐KI‐67 antibody), and biochemical recurrence (BCR) were investigated. Results KD of LATS2 increased the growth, migration, and invasion in LNCaP cells and only increased migration in PC3 cells. The expression of LATS2 was negatively associated with the grade group, T, N, M stage, and PI. In addition, the expression of LATS2 was a useful predictor of the histological effects of neoadjuvant hormonal therapy and BCR‐free survival periods. A multivariate analysis model including clinicopathological features showed that negative expression of LATS2 had a significantly higher risk of BCR (odds ratio = 2.95, P < 0.001). Conclusions LATS2 acts as a tumor suppressor in PC. LATS2 expression is a useful predictor for BCR. LATS2‐related activities are possibly dependent on the androgen‐dependency of PC cells. Therefore, we suggest that LATS2 could be a potential therapeutic target and a useful predictor for outcome in patients with PC.

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Pathological significance and prognostic role of LATS2 in prostate cancer

Cited by 4 publications

References 46 publications

Precision medicine targets for prostate cancers in African American men

Precision medicine targets for prostate cancers in African American men

Understanding human aging and the fundamental cell signaling link in age-related diseases: the middle-aging hypovascularity hypoxia hypothesis

Pathological significance and prognostic role of LATS2 in prostate cancer

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