LAT1 expression in colorectal cancer cells is unresponsive to HIF-1/2α accumulation under experimental hypoxia.

Autor: Ohgaki R; Department of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. ohgaki@pharma1.med.osaka-u.ac.jp.; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, 565-0871, Japan. ohgaki@pharma1.med.osaka-u.ac.jp., Hirase Y; Department of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Xu M; Department of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Okanishi H; Department of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Kanai Y; Department of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. ykanai@pharma1.med.osaka-u.ac.jp.; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, 565-0871, Japan. ykanai@pharma1.med.osaka-u.ac.jp.; Department of Metabolic Reprogramming and Signal Regulation, Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. ykanai@pharma1.med.osaka-u.ac.jp.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Aug 23; Vol. 14 (1), pp. 19635. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1038/s41598-024-70603-3
Abstrakt: L-type amino acid transporter 1 (LAT1) is upregulated in various cancer types and contributes to disease progression. Previous studies have demonstrated or suggested that hypoxia-inducible factors (HIFs), the key transcription factors in hypoxic responses, control the expression of LAT1 gene in several types of cancer cells. However, this regulatory relationship has not been investigated yet in colorectal cancer (CRC), one of the cancer types in which the increased LAT1 expression holds prognostic significance. In this study, we found that neither LAT1 mRNA nor protein is induced under hypoxic condition (1% O 2 ) in CRC HT-29 cells in vitro, regardless of the prominent HIF-1/2α accumulation and HIFs-dependent upregulation of glucose transporter 1. The hypoxic treatment generally did not increase either the mRNA or protein expression of LAT1 in eight CRC cell lines tested, in contrast to the pronounced upregulation by amino acid restriction. Interestingly, knockdown of von Hippel-Lindau ubiquitin ligase to inhibit the proteasomal degradation of HIFs caused an accumulation of HIF-2α and increased the LAT1 expression in certain CRC cell lines. This study contributes to delineating the molecular mechanisms responsible for the pathological expression of LAT1 in CRC cells, emphasizing the ambiguity of HIFs-dependent transcriptional upregulation of LAT1 across cancer cells.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje