Functional analysis of LAT3 in prostate cancer: Its downstream target and relationship with androgen receptor
| Autor: | Masahiro Sugiura, Maihulan Maimaiti, Yoshikatsu Kanai, Shinichi Sakamoto, Toru Hirota, Atsushi Kaneda, Norihisa Shindo, Minhui Xu, Ken Wakai, Keisuke Ando, Yusuke Imamura, Ayumu Fujimoto, Manato Kanesaka, Yuzuru Ikehara, Junryo Rii, Yasutaka Yamada, Naohiko Anzai, Tomohiko Ichikawa |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Genetics Genomics and Proteomics Cancer Research Bicalutamide Cell Survival Transfection amino acid transporter Cohort Studies Prostate cancer Cell Movement androgen receptor medicine Humans Amino acid transporter Separase Aged Cell Proliferation Prostatectomy Gene knockdown Cell growth Chemistry TOR Serine-Threonine Kinases Amino Acid Transport System y+L Prostatic Neoplasms LAT3 Dihydrotestosterone Original Articles General Medicine Middle Aged Prognosis prostate cancer medicine.disease Neoplasm Proteins Androgen receptor Oncology Receptors Androgen Gene Knockdown Techniques PC-3 Cells Disease Progression Cancer research Amino Acid Transport Systems Basic Original Article Immunostaining Protein Binding Signal Transduction medicine.drug |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 1347-9032 |
| DOI: | 10.1111/cas.14991 |
| Popis: | L‐type amino acid transporter 3 (LAT3, SLC43A1) is abundantly expressed in prostate cancer (PC) and is thought to play an essential role in PC progression through the cellular uptake of essential amino acids. Here, we analyzed the expression, function, and downstream target of LAT3 in PC. LAT3 was highly expressed in PC cells expressing androgen receptor (AR), and its expression was increased by dihydrotestosterone treatment and decreased by bicalutamide treatment. In chromatin immunoprecipitation sequencing of AR, binding of AR to the SLC43A1 region was increased by dihydrotestosterone stimulation. Knockdown of LAT3 inhibited cell proliferation, migration, and invasion, and the phosphorylation of p70S6K and 4EBP‐1. Separase (ESPL1) was identified as a downstream target of LAT3 by RNA sequencing analysis. In addition, immunostaining of prostatectomy specimens was performed. In the multivariate analysis, high expression of LAT3 was an independent prognostic factor for recurrence‐free survival (hazard ratio: 3.24; P = .0018). High LAT3 expression was correlated with the pathological T stage and a high International Society of Urological Pathology grade. In summary, our results suggest that LAT3 plays an important role in the progression of PC. LAT3 was highly expressed in PC cells expressing androgen receptor (AR), and in chromatin immunoprecipitation sequencing of AR, binding of AR to the SLC43A1 region was increased by dihydrotestosterone stimulation. Knockdown of LAT3 inhibited cell proliferation, migration, and invasion. High expression of LAT3 was significantly associated with poor prognosis (recurrence‐free survival; P = .0018). |
| Databáze: | OpenAIRE |
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