Aldolase A Enhances Intrahepatic Cholangiocarcinoma Proliferation and Invasion through Promoting Glycolysis

被引:26
作者
Li, Xiang [1 ,2 ]
Yu, Chang [2 ]
Luo, Yichun [2 ]
Lin, Jiacheng [2 ]
Wang, Fang [2 ]
Sun, Xuehua [2 ]
Gao, Yueqiu [2 ]
Tan, Weifeng [1 ]
Xia, Qiang [1 ]
Kong, Xiaoni [2 ]
机构
[1] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Hepat Surg, Shanghai, Peoples R China
[2] Shanghai Univ Chinese Tradit Med, ShuGuang Hosp, Dept Liver Dis, Cent Lab, 528 Zhangheng Rd, Shanghai 201203, Peoples R China
来源
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2021年 / 17卷 / 07期
基金
中国国家自然科学基金;
关键词
Intrahepatic Cholangiocarcinoma; Aldolase A; Metabolism Reprogram; Enzymatic Activity; Glycolysis; PYRUVATE-KINASE M2; GLUCOSE-METABOLISM; CANCER METABOLISM; LUNG-CANCER; CELL; ITACONATE; GROWTH; HIF-1-ALPHA; SUPPRESSES; EGFR;
D O I
10.7150/ijbs.59068
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Energy metabolism reprogramming has been implicated in tumorigenesis and development. Key metabolism enzyme Aldolase A (ALDOA) has been shown to be highly expressed and involved in various kinds of cancers including hepatocellular carcinoma. In this study, we found that ALDOA was highly expressed in clinical intrahepatic cholangiocarcinoma (ICC) tissues, and its high expression was negatively correlated with overall survival (OS) and recurrence-free survival (RFS) in ICC patients. Knockdown of ALDOA expression significantly inhibited the proliferation and migration of ICC both in vitro and in vivo, while highly-expressed ALDOA in ICC cells promoted the proliferation and migration of ICC cells. By applying ALDOA inhibitor and metabolic mass spectrometry tests, we demonstrated that ALDOA modulated the biological characteristics and metabolic level of ICC cells depending on its enzymatic activity. In summary, ALDOA promotes ICC proliferation and migration by enhancing ICC cells glycolysis. Blocking enzymatic activity of ALDOA provides a strategy to inhibit ICC.
引用
收藏
页码:1782 / 1794
页数:13
相关论文
共 49 条
  • [21] Fructose-bisphosphate aldolase A is a key regulator of hypoxic adaptation in colorectal cancer cells and involved in treatment resistance and poor prognosis
    Kawai, Kenji
    Uemura, Mamoru
    Munakata, Koji
    Takahashi, Hidekazu
    Haraguchi, Naotsugu
    Nishimura, Junichi
    Hata, Taishi
    Matsuda, Chu
    Ikenaga, Masakazu
    Murata, Kohei
    Mizushima, Tsuneicazu
    Yamamoto, Hirofumi
    Doki, Yuichiro
    Mori, Masaki
    [J]. INTERNATIONAL JOURNAL OF ONCOLOGY, 2017, 50 (02) : 525 - 534
  • [22] Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress
    Kim, Nam Hee
    Cha, Yong Hoon
    Lee, Jueun
    Lee, Seon-Hyeong
    Yang, Ji Hye
    Yun, Jun Seop
    Cho, Eunae Sandra
    Zhang, Xianglan
    Nam, Miso
    Kim, Nami
    Yuk, Young-Su
    Cha, So Young
    Lee, Yoonmi
    Ryu, Joo Kyung
    Park, Sunghyouk
    Cheong, Jae-Ho
    Kang, Sang Won
    Kim, Soo-Youl
    Hwang, Geum-Sook
    Yook, Jong In
    Kim, Hyun Sil
    [J]. NATURE COMMUNICATIONS, 2017, 8
  • [23] Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation
    Lampropoulou, Vicky
    Sergushichev, Alexey
    Bambouskova, Monika
    Nair, Sharmila
    Vincent, Emma E.
    Loginicheva, Ekaterina
    Cervantes-Barragan, Luisa
    Ma, Xiucui
    Huang, Stanley Ching-Cheng
    Griss, Takla
    Weinheimer, Carla J.
    Khader, Shabaana
    Randolph, Gwendalyn J.
    Pearce, Edward J.
    Jones, Russell G.
    Diwan, Abhinav
    Diamond, Michael S.
    Artyomov, Maxim N.
    [J]. CELL METABOLISM, 2016, 24 (01) : 158 - 166
  • [24] Identification of upregulated genes in oral squamous cell carcinomas
    Lessa, Roberta C.
    Campos, Antonio Hugo J. F. M.
    de Freitas, Carlos Elias
    da Silva, Felipe Rodrigues
    Kowalski, Luiz Paulo
    Carvalho, Andre Lopes
    Vettore, Andre Luiz
    [J]. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2013, 35 (10): : 1475 - 1481
  • [25] Transcriptional Regulation of the Warburg Effect in Cancer by SIX1
    Li, Ling
    Liang, Yingchun
    Kang, Lei
    Liu, Yang
    Gao, Shan
    Chen, Siyu
    Li, Ying
    You, Wenye
    Dong, Qian
    Hong, Tian
    Yan, Zhifeng
    Jin, Shuai
    Wang, Tao
    Zhao, Wei
    Mai, Haixing
    Huang, Jun
    Han, Xiao
    Ji, Quanbo
    Song, Qi
    Yang, Chao
    Zhao, Shixin
    Xu, Xiaojie
    Ye, Qinong
    [J]. CANCER CELL, 2018, 33 (03) : 368 - +
  • [26] 4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to exert anti-inflammatory effects
    Liao, Shan-Ting
    Han, Chao
    Xu, Ding-Qiao
    Fu, Xiao-Wei
    Wang, Jun-Song
    Kong, Ling-Yi
    [J]. NATURE COMMUNICATIONS, 2019, 10 (1)
  • [27] ORY-1001 Suppresses Cell Growth and Induces Apoptosis in Lung Cancer Through Triggering HK2 Mediated Warburg Effect
    Lu, Zhaoliang
    Guo, Yanke
    Zhang, Xiaoya
    Li, Jing
    Li, Leilei
    Zhang, Shuai
    Shan, Changliang
    [J]. FRONTIERS IN PHARMACOLOGY, 2018, 9
  • [28] Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma Systematic Review and Meta-analysis
    Mavros, Michael N.
    Economopoulos, Konstantinos P.
    Alexiou, Vangelis G.
    Pawlik, Timothy M.
    [J]. JAMA SURGERY, 2014, 149 (06) : 565 - 574
  • [29] Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1
    Mills, Evanna L.
    Ryan, Dylan G.
    Prag, Hiran A.
    Dikovskaya, Dina
    Menon, Deepthi
    Zaslona, Zbigniew
    Jedrychowski, Mark P.
    Costa, Ana S. H.
    Higgins, Maureen
    Hams, Emily
    Szpyt, John
    Runtsch, Marah C.
    King, Martin S.
    McGouran, Joanna F.
    Fischer, Roman
    Kessler, Benedikt M.
    McGettrick, Anne F.
    Hughes, Mark M.
    Carroll, Richard G.
    Booty, Lee M.
    Knatko, Elena V.
    Meakin, Paul J.
    Ashford, Michael L. J.
    Modis, Louise K.
    Brunori, Gino
    Sevin, Daniel C.
    Fallon, Padraic G.
    Caldwell, Stuart T.
    Kunji, Edmund R. S.
    Chouchani, Edward T.
    Frezza, Christian
    Dinkova-Kostova, Albena T.
    Hartley, Richard C.
    Murphy, Michael P.
    O'Neill, Luke A.
    [J]. NATURE, 2018, 556 (7699) : 113 - +
  • [30] The Emerging Hallmarks of Cancer Metabolism
    Pavlova, Natalya N.
    Thompson, Craig B.
    [J]. CELL METABOLISM, 2016, 23 (01) : 27 - 47