Oncogenic transformation of NIH/3T3 cells by the overexpression of L-type amino acid transporter 1, a promising anti-cancer target.

CD98 LAT1 NIH/3T3 monoclonal antibody oncogenicity

Journal

Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965

Informations de publication

Date de publication:
22 Jun 2021
Historique:
received: 26 04 2021
accepted: 26 05 2021
entrez: 1 7 2021
pubmed: 2 7 2021
medline: 2 7 2021
Statut: epublish

Résumé

L-type amino acid transporter 1 (LAT1)/SLC7A5 is the first identified CD98 light chain disulfide linked to the CD98 heavy chain (CD98hc/SLC3A2). LAT1 transports large neutral amino acids, including leucine, which activates mTOR, and is highly expressed in human cancers. We investigated the oncogenicity of human LAT1 introduced to NIH/3T3 cells by retrovirus infection. NIH/3T3 cell lines stably expressing human native (164C) or mutant (164S) LAT1 (naLAT1/3T3 or muLAT1/3T3, respectively) were established. We confirmed that endogenous mouse CD98hc forms a disulfide bond with exogenous human LAT1 in naLAT1/3T3, but not in muLAT1/3T3. Endogenous mouse CD98hc mRNA increased in both naNIH/3T3 and muLAT1/3T3, and a similar amount of exogenous human LAT1 protein was detected in both cell lines. Furthermore, naLAT1/3T3 and muLAT1/3T3 cell lines were evaluated for cell growth-related phenotypes (phosphorylation of ERK, cell-cycle progression) and cell malignancy-related phenotypes (anchorage-independent cell growth, tumor formation in nude mice). naLAT1/3T3 had stronger growth- and malignancy- related phenotypes than NIH/3T3 and muLAT1/3T3, suggesting the oncogenicity of native LAT1 through its interaction with CD98hc. Anti-LAT1 monoclonal antibodies significantly inhibited

Identifiants

pubmed: 34194623
doi: 10.18632/oncotarget.27981
pii: 27981
pmc: PMC8238248
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1256-1270

Informations de copyright

Copyright: © 2021 Hayashi et al.

Déclaration de conflit d'intérêts

CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.

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Auteurs

Natsumi Hayashi (N)

Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, Higashiosaka-Shi, Osaka, Japan.
Cell Biology Laboratory, School of Pharmacy, Kindai University, Osaka, Japan.
Co-first authors.
This laboratory (April, 2000~) was closed at the end of March, 2020, after the mandatory retirement of Takashi Masuko.

Akitaka Yamasaki (A)

Cell Biology Laboratory, School of Pharmacy, Kindai University, Osaka, Japan.
Laboratory of Oncology Pharmacy Practice and Science, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai-Shi, Miyagi, Japan.
Co-first authors.
This laboratory (April, 2000~) was closed at the end of March, 2020, after the mandatory retirement of Takashi Masuko.

Shiho Ueda (S)

Cell Biology Laboratory, School of Pharmacy, Kindai University, Osaka, Japan.

Shogo Okazaki (S)

Division of Cell Fate Regulation, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda-shi, Chiba, Japan.

Yoshiya Ohno (Y)

Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe-Shi, Hyogo, Japan.

Toshiyuki Tanaka (T)

Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe-Shi, Hyogo, Japan.

Yuichi Endo (Y)

Natural Drug Resources, Faculty of Pharmacy, Kindai University, Osaka, Japan.

Yoshihisa Tomioka (Y)

Laboratory of Oncology Pharmacy Practice and Science, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai-Shi, Miyagi, Japan.

Kazue Masuko (K)

Cell Biology Laboratory, School of Pharmacy, Kindai University, Osaka, Japan.

Takashi Masuko (T)

Cell Biology Laboratory, School of Pharmacy, Kindai University, Osaka, Japan.
Natural Drug Resources, Faculty of Pharmacy, Kindai University, Osaka, Japan.

Reiko Sugiura (R)

Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, Higashiosaka-Shi, Osaka, Japan.

Classifications MeSH