Evidence map›Paper›PMID 31527549›Full record

ArticleCancers2019

CYP17A1 Maintains the Survival of Glioblastomas by Regulating SAR1-Mediated Endoplasmic Reticulum Health and Redox Homeostasis.

Hong-Yi Lin, Chiung-Yuan Ko, Tzu-Jen Kao, Wen-Bin Yang, Yu-Ting Tsai, Jian-Ying Chuang, Siou-Lian Hu, Pei-Yu Yang, Wei-Lun Lo, Tsung-I Hsu

Open access · goldAbstract read
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. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

19 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
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  6. Progesterone boosts abiraterone-driven target and NK cell therapies against glioblastoma.Journal of experimental & clinical cancer research : CR · 2024
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  15. Hijacking Sexual Immuno-Privilege in GBM-An Immuno-Evasion Strategy.International journal of molecular sciences · 2021
    Article
  16. Steroidogenic cytochrome P450 17A1 structure and function.Molecular and cellular endocrinology · 2021
    Review
  17. Review
  18. Review
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Hong-Yi LinGraduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, 11031 Taipei, Taiwan. d620105002@tmu.edu.tw.
Chiung-Yuan KoGraduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, 11031 Taipei, Taiwan. ko680108@tmu.edu.tw.
Tzu-Jen KaoGraduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, 11031 Taipei, Taiwan. geokao@tmu.edu.tw.
Wen-Bin YangGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. geniusbing@gmail.com.
Yu-Ting TsaiGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. terry1992@gmail.com.
Jian-Ying ChuangGraduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, 11031 Taipei, Taiwan. chuangcy@tmu.edu.tw.
Siou-Lian HuGraduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, 11031 Taipei, Taiwan. everywheresmile@gmail.com.
Pei-Yu YangGraduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, 11031 Taipei, Taiwan. peggy80123@hotmail.com.
Wei-Lun LoGraduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, 11031 Taipei, Taiwan. 12317@s.tmu.edu.tw.
Tsung-I HsuGraduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, 11031 Taipei, Taiwan. dabiemhsu@tmu.edu.tw.
National Health Research Institutes · TWTaipei Medical University · TW

Funding

Ministry of Science and Technology, Taiwan MOST 106-2320-B-038-003-MY2Ministry of Science and Technology, Taiwan MOST 108-2628-B-038-005-
6 · The paper itself

Abstract

Cytochrome P450 (CYP) 17A1 is an important steroidogenic enzyme harboring 17α-hydroxylase and performing 17,20 lyase activities in multiple steps of steroid hormone synthesis, including dehydroepiandrosterone (DHEA) biosynthesis. Previously, we showed that CYP17A1-mediated DHEA production clearly protects glioblastomas from temozolomide-induced apoptosis, leading to drug resistance. Herein, we attempt to clarify whether the inhibition of CYP17A1 has a tumor-suppressive effect, and to determine the steroidogenesis-independent functions of CYP17A1 in glioblastomas. Abiraterone, an inhibitor of CYP17A1, significantly inhibits the proliferation of A172, T98G, and PT#3 (the primary glioblastoma cells) by inducing apoptosis. In parallel, abiraterone potently suppresses tumor growth in mouse models through transplantation of PT#3 cells to the back or to the brain. Based on evidence that abiraterone induces endoplasmic reticulum (ER) stress, followed by the accumulation of reactive oxygen species (ROS), CYP17A1 is important for ER health and redox homeostasis. To confirm our hypothesis, we showed that CYP17A1 overexpression prevents the initiation of ER stress and attenuates ROS production by regulating SAR1a/b expression. Abiraterone dissociates SAR1a/b from ER-localized CYP17A1, and induces SAR1a/b ubiquitination, leading to degradation. Furthermore, SAR1 overexpression rescues abiraterone-induced apoptosis and impairs redox homeostasis. In addition to steroid hormone synthesis, CYP17A1 associates with SAR1a/b to regulate protein processing and maintain ER health in glioblastomas.

Indexed as

abirateroneCYP17A1glioblastomaSAR1

Identifiers

PMID31527549
PMCPMC6770831
OpenAlexW2974305135

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.