Evidence map›Paper›PMID 41549123›Full record

ArticleHypertension research : official journal of the Japanese Society of Hypertension2026

Angiotensin II type 1 receptor signaling promotes bladder cancer progression and its inhibition by Losartan.

Ryoken Yamanaka, Kento Miura, Norimasa Yamasaki, Sawako Ogata, Megmi Nakamura, Toshiya Inaba, Anarkhuu Bold-Erdene, Uyanga Enkhbaatar, Fatemeh Beygom Mirkatouli, Shuka Miura and 11 more

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Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Ryoken YamanakaDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Kento MiuraDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Norimasa YamasakiDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Sawako OgataDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Megmi NakamuraDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Toshiya InabaDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Anarkhuu Bold-ErdeneDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Uyanga EnkhbaatarDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Fatemeh Beygom MirkatouliDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Shuka MiuraDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Naohisa HosomiDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Kohei KobatakeDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Kenshiro TakemotoDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Yuki KohadaDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Ryo TasakaDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Tomoya HatayamaDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Kazuma YukihiroDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Hiroyuki ShikumaDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Kyosuke IwaneDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Nobuyuki HinataDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Osamu KaminumaDepartment of Disease Models, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. okami@hiroshima-u.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The renin-angiotensin system (RAS) plays a central role in regulating blood pressure and has recently been implicated in cancer biology. Although angiotensin II (AngII) receptor blockers (ARBs) have shown clinical benefit in bladder cancer, their mechanisms of action remain unclear. Here, we investigated the contribution of AngII type 1 receptor (AGTR1) to bladder cancer progression and assessed the therapeutic potential of the ARB losartan (LOS). In patients with primary non-muscle-invasive bladder cancer, intravesical recurrence following transurethral tumor resection correlated with AGTR1 expression levels. Public database analysis revealed that the expression of AGTR1 and its downstream kinases, extracellular signal-regulated kinase (ERK) 1 and ERK2, was associated with overall survival in bladder urothelial carcinoma. In AGTR1-overexpressing T24 bladder cancer cells, AngII promoted invasion and migration and upregulated neuronal nitric oxide synthase, without affecting proliferation. These effects were accompanied by rapid ERK phosphorylation alongside Akt dephosphorylation. RNA sequencing revealed that AGTR1 expression and AngII stimulation activated NF-κB, mTOR, and epithelial-mesenchymal transition (EMT) pathways. LOS suppressed these AngII-mediated responses, whereas the AngII-independent upregulation of EMT-related proteins and the enhancement of mitochondrial energy metabolism by AngII in AGTR1-overexpressing cells remained unaffected. In vivo, AGTR1 facilitated early tumor engraftment and promoted tumor progression, accompanied by reduced E-cadherin and elevated N-cadherin expression, with most of these changes suppressed by LOS treatment. In conclusion, our findings highlight the crucial role of AGTR1 in bladder cancer and support the repositioning of ARBs, such as LOS, as therapeutics for AGTR1-upregulated bladder cancer, while underscoring the importance of AGTR1 stratification for future clinical evaluation.

Indexed as

Angiotensin II Type 1 Receptor BlockersLosartanReceptor, Angiotensin, Type 1Urinary Bladder NeoplasmsAnimalsCell Line, TumorDisease ProgressionFemaleHumansMaleNon-Muscle Invasive Bladder NeoplasmsSignal TransductionAGTR1 protein, humanAngiotensin II Type 1 Receptor BlockersLosartanReceptor, Angiotensin, Type 1Angiotensin IIAngiotensin II type 1 receptorBladder cancerImplemental hypertensionLosartan

Identifiers

PMID41549123
PMCPMC13050642

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.