Cationic amino acid transporter PQLC2 is a potential therapeutic target in gastric cancer

被引:7
|
作者
Jeung, Yun-Ji [1 ,2 ]
Lee, Kyeong [3 ]
Lee, Hyo Jin [4 ]
Kim, Eunah [5 ]
Son, Myung Jin [5 ,6 ]
Ahn, Jiwon [1 ]
Kim, Han-Gyeul [1 ,6 ]
Kim, Wantae [1 ]
Lee, Ho-Joon [5 ]
Kim, Jin Man [4 ]
Chung, Kyung-Sook [1 ,5 ,6 ]
机构
[1] KRIBB, Biomed Translat Res Ctr, Daejeon, South Korea
[2] Chungnam Natl Univ, Coll Med, Dept Pathol & Med Sci, Daejeon, South Korea
[3] Dongguk Univ Seoul, Coll Pharm, Goyang, South Korea
[4] Chungnam Natl Univ, Coll Med, Dept Internal Med, Daejeon, South Korea
[5] KRIBB, Stem Cell Convergence Res Ctr, Daejeon, South Korea
[6] Korea Univ Sci & Technol UST, KRIBB Sch Biosci, Dept Funct Genom, Daejeon, South Korea
基金
新加坡国家研究基金会;
关键词
gastric cancer; metastasis; PQLC2; therapeutic target; tumor formation; PROTEIN; CHEMOTHERAPY; EXPRESSION; CYSTINOSIS; PATHWAYS; SLC38A9; FUTURE; GENE;
D O I
10.1111/cas.13966
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumor cells overexpress amino acid transporters to meet the increased demand for amino acids. PQ loop repeat-containing (PQLC)2 is a cationic amino acid transporter that might be involved in cancer progression. Here, we show that upregulation of PQLC2 is critical to gastric cancer (GC) development in vitro and in vivo. Both PQLC2 mRNA and protein were overexpressed in GC tissues, especially of the diffuse type. Overexpression of PQLC2 promoted cell growth, anchorage independence, and tumor formation in nude mice. This was due to activation of MEK/ERK1/2 and PI3K/AKT signaling. Conversely, PQLC2 knockdown caused growth arrest and cell death of cancer cells and suppressed tumor growth in a mouse xenograft model. These results suggest that targeting PQLC2 is an effective strategy for GC treatment.
引用
收藏
页码:1453 / 1463
页数:11
相关论文
共 50 条
  • [1] Receptor-like role for PQLC2 amino acid transporter in the lysosomal sensing of cationic amino acids
    Talaia, Gabriel
    Amick, Joseph
    Ferguson, Shawn M.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 118 (08)
  • [2] Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy
    Jezegou, Adrien
    Llinares, Elisa
    Anne, Christine
    Kieffer-Jaquinod, Sylvie
    O'Regan, Seana
    Aupetit, Joelle
    Chabli, Allel
    Sagne, Corinne
    Debacker, Cecile
    Chadefaux-Vekemans, Bernadette
    Journet, Agnes
    Andre, Bruno
    Gasnier, Bruno
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (50) : E3434 - E3443
  • [3] PQLC2 recruits the C9orf72 complex to lysosomes in response to cationic amino acid starvation
    Amick, Joseph
    Tharkeshwar, Arun Kumar
    Talaia, Gabriel
    Ferguson, Shawn M.
    JOURNAL OF CELL BIOLOGY, 2020, 219 (01):
  • [4] ENDOTHELIAL CATIONIC AMINO ACID TRANSPORTER 1: A POTENTIAL NEW THERAPUTIC TARGET IN HYPERTENSION
    Rajapakse, N. W.
    Konstantinidis, G.
    Head, G. A.
    Evans, R. G.
    Nguyen-Huu, T.
    Kaye, D. M.
    HYPERTENSION, 2012, 60 (02) : 499 - 499
  • [5] Arginine-selective modulation of the lysosomal transporter PQLC2 through a gate-tuning mechanism
    Leray, Xavier
    Conti, Rossella
    Li, Yan
    Debacker, Cecile
    Castelli, Florence
    Fenaille, Francois
    Zdebik, Anselm A.
    Pusch, Michael
    Gasnier, Bruno
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 118 (32)
  • [6] Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy (vol 109, pg E3434, 2012)
    Jezegou, Adrien
    Llinares, Elisa
    Anne, Christine
    Kieffer-Jaquinod, Sylvie
    O'Regan, Seana
    Aupetit, Joelle
    Chabli, Allel
    Sagne, Corinne
    Debacker, Cecile
    Chadefaux-Vekemans, Bernadette
    Journet, Agnes
    Andre, Bruno
    Gasnier, Bruno
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (08) : 3197 - 3197
  • [7] Amino acid transporter inhibitors: Their therapeutic potential
    Kanai, Y
    Endou, H
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2005, 97 : 24P - 24P
  • [8] L-type Amino Acid Transporter 1 as a Therapeutic Target in Pancreatic Cancer
    Norrsell, Ragnar
    Bauden, Monika
    Andersson, Roland
    Ansari, Daniel
    CANCER CONTROL, 2024, 31
  • [9] cMET as a potential therapeutic target in gastric cancer
    Teng, Lisong
    Lu, Jun
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2013, 32 (06) : 1247 - 1254
  • [10] POSTN: a Potential Therapeutic Target in the Treatment of Gastric Cancer?
    Yu, Hui-Chuang
    Guo, Hong-Mei
    JOURNAL OF GASTROINTESTINAL SURGERY, 2023, 27 (06) : 1294 - 1294