Evidence map›Paper›PMID 31212816›Full record

ArticleCancers2019

Hexokinase 2 Regulates Ovarian Cancer Cell Migration, Invasion and Stemness via FAK/ERK1/2/MMP9/NANOG/SOX9 Signaling Cascades.

Michelle K Y Siu, Yu-Xin Jiang, Jing-Jing Wang, Thomas H Y Leung, Chae Young Han, Benjamin K Tsang, Annie N Y Cheung, Hextan Y S Ngan, Karen K L Chan

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
6.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 136 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Role of SOX9 protein in ovarian carcinoma: A molecular insight.The Indian journal of medical research · 2026
    Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Hexokinase 2 promotes tumor development and progression.American journal of cancer research · 2025
    Review
  20. Review

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Michelle K Y SiuDepartment of Obstetrics and Gynecology, University of Hong Kong, Hong Kong, China. mkysiu@gmail.com.
Yu-Xin JiangDepartment of Obstetrics and Gynecology, University of Hong Kong, Hong Kong, China. yuxin_jiang2012@126.com.
Jing-Jing WangDepartment of Obstetrics and Gynecology, University of Hong Kong, Hong Kong, China. wjj01947@connect.hku.hk.
Thomas H Y LeungDepartment of Obstetrics and Gynecology, University of Hong Kong, Hong Kong, China. thyl@hku.hk.
Chae Young HanDepartment of Obstetrics and Gynecology and Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada. lemon7time@gmail.com.
Benjamin K TsangDepartment of Obstetrics and Gynecology and Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada. btsang@ohri.c.
Annie N Y CheungDepartment of Pathology, University of Hong Kong, Hong Kong, China. anycheun@pathology.hku.hk.ORCID 0000-0002-1584-7568
Hextan Y S NganDepartment of Obstetrics and Gynecology, University of Hong Kong, Hong Kong, China. hysngan@hku.hk.
Karen K L ChanDepartment of Obstetrics and Gynecology, University of Hong Kong, Hong Kong, China. kklchan@hku.hk.
University of Hong Kong · HKMacau University of Science and Technology · MOUniversity of Ottawa · CA

Funding

Hong Kong Research Grants Council General Research Fund HKU 17101414University Research Committee, University of Hong Kong 201511159173
6 · The paper itself

Abstract

Metabolic reprogramming is a common phenomenon in cancers. Thus, glycolytic enzymes could be exploited to selectively target cancer cells in cancer therapy. Hexokinase 2 (HK2) converts glucose to glucose-6-phosphate, the first committed step in glucose metabolism. Here, we demonstrated that HK2 was overexpressed in ovarian cancer and displayed significantly higher expression in ascites and metastatic foci. HK2 expression was significantly associated with advanced stage and high-grade cancers, and was an independent prognostic factor. Functionally, knockdown of HK2 in ovarian cancer cell lines and ascites-derived tumor cells hindered lactate production, cell migration and invasion, and cell stemness properties, along with reduced FAK/ERK1/2 activation and metastasis- and stemness-related genes. 2-DG, a glycolysis inhibitor, retarded cell migration and invasion and reduced stemness properties. Inversely, overexpression of HK2 promoted cell migration and invasion through the FAK/ERK1/2/MMP9 pathway, and enhanced stemness properties via the FAK/ERK1/2/NANOG/SOX9 cascade. HK2 abrogation impeded in vivo tumor growth and dissemination. Notably, ovarian cancer-associated fibroblast-derived IL-6 contributed to its up-regulation. In conclusion, HK2, which is regulated by the tumor microenvironment, controls lactate production and contributes to ovarian cancer metastasis and stemness regulation via FAK/ERK1/2 signaling pathway-mediated MMP9/NANOG/SOX9 expression. HK2 could be a potential prognostic marker and therapeutic target for ovarian cancer.

Indexed as

FAK/ERK signalingHK2metastasisovarian cancerstemness

Identifiers

PMID31212816
PMCPMC6627345
OpenAlexW2951540630

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.