Evidence map›Paper›PMID 32205868›Full record

ArticleOncogene2020

Muscarinic receptors promote castration-resistant growth of prostate cancer through a FAK-YAP signaling axis.

Yusuke Goto, Toshinori Ando, Hiroki Izumi, Xiaodong Feng, Nadia Arang, Mara Gilardi, Zhiyong Wang, Kazuyo Ando, J Silvio Gutkind

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.7field-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

27 citing papers in PubMed, 41 citations in OpenAlex.

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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

9 authors at 4 institutions in 3 countries.

Yusuke GotoMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Toshinori AndoMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Hiroki IzumiMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Xiaodong FengMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Nadia ArangMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Mara GilardiMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Zhiyong WangMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Kazuyo AndoMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
J Silvio GutkindMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA. sgutkind@health.ucsd.edu.ORCID http://orcid.org/0000-0002-5150-4482
University of California San Diego · USHiroshima University · JPSichuan University · CNUC San Diego Health System · US

Funding

Area C: Genome-wide identification and targeting of resistance to cancer therapyR33CA225291 · NCI · UNIV OF MARYLAND, COLLEGE PARK · PI GUTKIND, JORGE SILVIO, RUPPIN, EYTAN · 2017 to 2017
$1.5M
Super-resolution confocal microscopeS10OD021831 · OD · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI LEY, KLAUS F. · 2017 to 2017
$566k
NCI NIH HHS R33 CA225291NIH HHS S10 OD021831
6 · The paper itself

Abstract

Prostate cancer (PCa) innervation contributes to the progression of PCa. However, the precise impact of innervation on PCa cells is still poorly understood. By focusing on muscarinic receptors, which are activated by the nerve-derived neurotransmitter acetylcholine, we show that muscarinic receptors 1 and 3 (m1 and m3) are highly expressed in PCa clinical specimens compared with all other cancer types, and that amplification or gain of their corresponding encoding genes (CHRM1 and CHRM3, respectively) represent a worse prognostic factor for PCa progression free survival. Moreover, m1 and m3 gene gain or amplification is frequent in castration-resistant PCa (CRPC) compared with hormone-sensitive PCa (HSPC) specimens. This was reflected in HSPC-derived cells, which show aberrantly high expression of m1 and m3 under androgen deprivation mimicking castration and androgen receptor inhibition. We also show that pharmacological activation of m1 and m3 signaling is sufficient to induce the castration-resistant growth of PCa cells. Mechanistically, we found that m1 and m3 stimulation induces YAP activation through FAK, whose encoding gene, PTK2 is frequently amplified in CRPC cases. Pharmacological inhibition of FAK and knockdown of YAP abolished m1 and m3-induced castration-resistant growth of PCa cells. Our findings provide novel therapeutic opportunities for muscarinic-signal-driven CRPC progression by targeting the FAK-YAP signaling axis.

Indexed as

Signal TransductionAdaptor Proteins, Signal TransducingFocal Adhesion Kinase 1HumansMaleNeoplasm ProteinsPC-3 CellsProstatic Neoplasms, Castration-ResistantReceptor, Muscarinic M1Receptor, Muscarinic M3Transcription FactorsYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingCHRM1 protein, humanCHRM3 protein, humanFocal Adhesion Kinase 1Neoplasm ProteinsPTK2 protein, humanReceptor, Muscarinic M1Receptor, Muscarinic M3Transcription FactorsYAP1 protein, humanYAP-Signaling Proteins

Identifiers

PMID32205868
PMCPMC7428076
OpenAlexW3012682077

What OpenQuestion holds

Textmetadata
LicenceTDM
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.