Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma Article Swipe
Maihulan Maimaiti
,
Shinichi Sakamoto
,
Yasutaka Yamada
,
Masahiro Sugiura
,
Junryo Rii
,
Nobuyoshi Takeuchi
,
Yusuke Imamura
,
Tomomi Furihata
,
Keisuke Ando
,
Kosuke Higuchi
,
Minhui Xu
,
Tomokazu Sazuka
,
Kazuyoshi Nakamura
,
Atsushi Kaneda
,
Yoshikatsu Kanai
,
Natasha Kyprianou
,
Yuzuru Ikehara
,
Naohiko Anzai
,
Tomohiko Ichikawa
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-020-58136-x
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-020-58136-x
L-type amino acid transporter 1 (LAT1) plays a role in transporting essential amino acids including leucine, which regulates the mTOR signaling pathway. Here, we studied the expression profile and functional role of LAT1 in bladder cancer. Furthermore, the pharmacological activity of JPH203, a specific inhibitor of LAT1, was studied in bladder cancer. LAT1 expression in bladder cancer cells was higher than that in normal cells. SiLAT1 and JPH203 suppressed cell proliferative and migratory and invasive abilities in bladder cancer cells. JPH203 inhibited leucine uptake by > 90%. RNA-seq analysis identified insulin-like growth factor-binding protein-5 (IGFBP-5) as a downstream target of JPH203. JPH203 inhibited phosphorylation of MAPK / Erk, AKT, p70S6K and 4EBP-1. Multivariate analysis revealed that high LAT1 expression was found as an independent prognostic factor for overall survival (HR3.46 P = 0.0204). Patients with high LAT1 and IGFBP-5 expression had significantly shorter overall survival periods than those with low expression (P = 0.0005). High LAT1 was related to the high Grade, pathological T stage, LDH, and NLR. Collectively, LAT1 significantly contributed to bladder cancer progression. Targeting LAT1 by JPH203 may represent a novel therapeutic option in bladder cancer treatment.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41598-020-58136-x
- https://www.nature.com/articles/s41598-020-58136-x.pdf
- OA Status
- gold
- Cited By
- 118
- References
- 44
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3003241498
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3003241498Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41598-020-58136-xDigital Object Identifier
- Title
-
Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinomaWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-01-28Full publication date if available
- Authors
-
Maihulan Maimaiti, Shinichi Sakamoto, Yasutaka Yamada, Masahiro Sugiura, Junryo Rii, Nobuyoshi Takeuchi, Yusuke Imamura, Tomomi Furihata, Keisuke Ando, Kosuke Higuchi, Minhui Xu, Tomokazu Sazuka, Kazuyoshi Nakamura, Atsushi Kaneda, Yoshikatsu Kanai, Natasha Kyprianou, Yuzuru Ikehara, Naohiko Anzai, Tomohiko IchikawaList of authors in order
- Landing page
-
https://doi.org/10.1038/s41598-020-58136-xPublisher landing page
- PDF URL
-
https://www.nature.com/articles/s41598-020-58136-x.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41598-020-58136-x.pdfDirect OA link when available
- Concepts
-
Bladder cancer, Leucine, Protein kinase B, Cancer research, Medicine, PI3K/AKT/mTOR pathway, Cancer, Amino acid, MAPK/ERK pathway, Internal medicine, Biology, Phosphorylation, Signal transduction, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
118Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 71, 2023: 15, 2022: 9, 2021: 9Per-year citation counts (last 5 years)
- References (count)
-
44Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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