Evidence map›Paper›PMID 37210546›Full record

ArticleJournal of experimental & clinical cancer research : CR2023

Targeting PHB1 to inhibit castration-resistant prostate cancer progression in vitro and in vivo.

Junmei Liu, Ranran Zhang, Tong Su, Qianqian Zhou, Lin Gao, Zongyue He, Xin Wang, Jian Zhao, Yuanxin Xing, Feifei Sun and 7 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. 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

17 authors at 4 institutions in 2 countries.

Junmei Liu *Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Ranran Zhang *The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Tong SuThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Qianqian ZhouThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Lin GaoThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Zongyue HeThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Xin WangThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Jian ZhaoDepartment of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, China.
Yuanxin XingResearch Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, China.
Feifei SunThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Wenjie CaiThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Xinpei WangThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Jingying HanSchool of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Ruixi QinDepartment of Pathology, Qilu Hospital of Shandong University, Jinan, China.
Laurent DésaubryINSERM, UMR 1260, Regenerative Nanomedicine, University of Strasbourg, FMTS (Fédération de Médecine Translationnelle de L'Université de Strasbourg), Strasbourg, France.
Bo HanThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China. boh@sdu.edu.cn.
Weiwen ChenDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China. chenweiwen@sdu.edu.cn.ORCID http://orcid.org/0000-0001-7895-4101
Shandong University · CNQilu Hospital of Shandong University · CNInserm · FRJinan Central Hospital · CN

Funding

Key Technology Research and Development Program of Shandong 2019GSF108076National Natural Science Foundation of China 81972413National Natural Science Foundation of China 81972416National Natural Science Foundation of China 82172818Natural Science Foundation of Shandong Province ZR2018MH025Natural Science Foundation of Shandong Province ZR2018MH030Natural Science Foundation of Shandong Province ZR2022MH317
6 · The paper itself

Abstract

backgroundCastration-resistant prostate cancer (CRPC) is currently the main challenge for prostate cancer (PCa) treatment, and there is an urgent need to find novel therapeutic targets and drugs. Prohibitin (PHB1) is a multifunctional chaperone/scaffold protein that is upregulated in various cancers and plays a pro-cancer role. FL3 is a synthetic flavagline drug that inhibits cancer cell proliferation by targeting PHB1. However, the biological functions of PHB1 in CRPC and the effect of FL3 on CRPC cells remain to be explored.

methodsSeveral public datasets were used to analyze the association between the expression level of PHB1 and PCa progression as well as outcome in PCa patients. The expression of PHB1 in human PCa specimens and PCa cell lines was examined by immunohistochemistry (IHC), qRT-PCR, and Western blot. The biological roles of PHB1 in castration resistance and underlying mechanisms were investigated by gain/loss-of-function analyses. Next, in vitro and in vivo experiments were conducted to investigate the anti-cancer effects of FL3 on CRPC cells as well as the underlying mechanisms.

resultsPHB1 expression was significantly upregulated in CRPC and was associated with poor prognosis. PHB1 promoted castration resistance of PCa cells under androgen deprivation condition. PHB1 is an androgen receptor (AR) suppressive gene, and androgen deprivation promoted the PHB1 expression and its nucleus-cytoplasmic translocation. FL3, alone or combined with the second-generation anti-androgen Enzalutamide (ENZ), suppressed CRPC cells especially ENZ-sensitive CRPC cells both in vitro and in vivo. Mechanically, we demonstrated that FL3 promoted trafficking of PHB1 from plasma membrane and mitochondria to nucleus, which in turn inhibited AR signaling as well as MAPK signaling, yet promoted apoptosis in CRPC cells.

conclusionOur data indicated that PHB1 is aberrantly upregulated in CRPC and is involved in castration resistance, as well as providing a novel rational approach for treating ENZ-sensitive CRPC.

Indexed as

Prostatic Neoplasms, Castration-ResistantAndrogen AntagonistsBenzamidesCell Line, TumorCell ProliferationHumansMaleNitrilesPhenylthiohydantoinProhibitinsReceptors, AndrogenAndrogen AntagonistsBenzamidesenzalutamideNitrilesPhenylthiohydantoinProhibitinsReceptors, AndrogenCRPCEnzalutamideFL3Prohibitin

Identifiers

PMID37210546
PMCPMC10199526
OpenAlexW4377157356

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.