PMID- 33042622
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201013
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 10
IP  - 9
DP  - 2020
TI  - Human haptoglobin contributes to breast cancer oncogenesis through glycolytic 
      activity modulation.
PG  - 2865-2877
AB  - Cellular metabolism reprogramming is a hallmark in cancers including breast 
      cancer. Switching off the glycolytic energy in cancer has been indicated as one 
      of the anti-cancer strategies. Aberrant haptoglobin (HP) expression has been 
      shown to cause metabolic dysfunction and implicated in different malignancies. 
      However, its roles in breast cancer and glycolysis remain elusive. Here, we 
      reported HP was upregulated in breast cancer tissues and the circulation. HP 
      conferred oncogenic roles by regulating cell cycle progression and apoptosis in 
      breast cancer cells. Further analysis identified the correlation between HP and 
      glycolytic enzymes such as glucose-6-phosphate isomerase (GPI) and hexokinase 
      (HK). Glycolytic activities were altered upon HP knockdown which were confirmed 
      by glucose uptake and LDH activity assays. GPI was found to be downstream 
      effector of HP while knockdown of GPI led to decreased glycolytic activity and 
      restored oxygen consumption. GPI silencing decreased cell migration/invasion 
      ability and sensitized breast cancer cells to chemo-drug. Moreover, animal study 
      suggested inhibition of both HP and GPI significantly impeded tumor growth in 
      mice. Collectively, we report for the first time the oncogenic roles of HP, at 
      least partially, through regulating glycolysis and its downstream effector, GPI, 
      contributes in maintaining EMT and chemoresistance in breast cancer.
CI  - AJCR Copyright (c) 2020.
FAU - Chen, Jiawei
AU  - Chen J
AD  - Department of Surgery, The University of Hong Kong and The University of Hong 
      Kong-Shenzhen Hospital China.
FAU - Cheuk, Isabella Wai-Yin
AU  - Cheuk IW
AD  - Department of Surgery, The University of Hong Kong and The University of Hong 
      Kong-Shenzhen Hospital China.
FAU - Siu, Man-Ting
AU  - Siu MT
AD  - Department of Surgery, The University of Hong Kong and The University of Hong 
      Kong-Shenzhen Hospital China.
FAU - Yang, Weiqin
AU  - Yang W
AD  - School of Biomedical Sciences, The Chinese University of Hong Kong Hong Kong SAR, 
      China.
FAU - Cheng, Alfred Sl
AU  - Cheng AS
AD  - School of Biomedical Sciences, The Chinese University of Hong Kong Hong Kong SAR, 
      China.
FAU - Shin, Vivian Yvonne
AU  - Shin VY
AD  - Department of Surgery, The University of Hong Kong and The University of Hong 
      Kong-Shenzhen Hospital China.
FAU - Kwong, Ava
AU  - Kwong A
AD  - Department of Surgery, The University of Hong Kong and The University of Hong 
      Kong-Shenzhen Hospital China.
AD  - Department of Surgery, The Hong Kong Sanatorium and Hospital Hong Kong SAR, 
      China.
AD  - The Hong Kong Hereditary Breast Cancer Family Registry Hong Kong SAR, China.
LA  - eng
PT  - Journal Article
DEP - 20200901
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC7539774
OTO - NOTNLM
OT  - GPI
OT  - Haptoglobin
OT  - breast cancer
OT  - glycolysis
COIS- None.
EDAT- 2020/10/13 06:00
MHDA- 2020/10/13 06:01
PMCR- 2020/09/01
CRDT- 2020/10/12 05:31
PHST- 2020/01/17 00:00 [received]
PHST- 2020/03/09 00:00 [accepted]
PHST- 2020/10/12 05:31 [entrez]
PHST- 2020/10/13 06:00 [pubmed]
PHST- 2020/10/13 06:01 [medline]
PHST- 2020/09/01 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2020 Sep 1;10(9):2865-2877. eCollection 2020.