Evidence mapPaperPMID 35895804Full record

ArticleAutophagy2023

TNK2/ACK1-mediated phosphorylation of ATP5F1A (ATP synthase F1 subunit alpha) selectively augments survival of prostate cancer while engendering mitochondrial vulnerability.

Surbhi Chouhan, Mithila Sawant, Cody Weimholt, Jingqin Luo, Robert W Sprung, Mailyn Terrado, David M Mueller, H Shelton Earp, Nupam P Mahajan

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06705686 (Phase 1 First in Human Trial to Assess Safety and Tolerability of the Novel ACK1 Inhibitor), which is not on this map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.5field-weighted citation impact, top 4% 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.

NCT06705686 phase1recruitingnot on this mapstarted 2026, after this paper: background citation

Phase 1 First in Human Trial to Assess Safety and Tolerability of the Novel ACK1 Inhibitor (R)-9b in Patients With Prostate Cancer

TypeinterventionalSponsorTechnoGenesys, Inc.Ran2026 to 2028Enrolled40ConditionsMetastatic Castration-resistant Prostate Cancer (CRPC), Metastatic Castration-resistant Prostate CarcinomaArms(R)-9bMS
3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
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  3. Review
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  10. Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025
    Review
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  12. Article
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  14. Review
  15. Article
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  18. Review
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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 3 institutions in 1 country.

Surbhi ChouhanDepartment of Surgery, Cancer Research Building, St. Louis, MO, USA.
Mithila SawantDepartment of Surgery, Cancer Research Building, St. Louis, MO, USA.
Cody WeimholtDepartment of Pathology & Immunology Washington University, St. Louis, MO, USA.
Jingqin LuoDivision of Public Health Sciences, Washington University, St. Louis, MO, USA.
Robert W SprungDepartment of Surgery, Cancer Research Building, St. Louis, MO, USA.
Mailyn TerradoCenter for Genetic Diseases, Chicago Medical School, Rosalind Franklin University, North Chicago, IL, USA.
David M MuellerCenter for Genetic Diseases, Chicago Medical School, Rosalind Franklin University, North Chicago, IL, USA.
H Shelton EarpLineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
Nupam P MahajanDepartment of Surgery, Cancer Research Building, St. Louis, MO, USA.ORCID 0000-0002-4150-602X
Washington University in St. Louis · USRosalind Franklin University of Medicine and Science · USUniversity of North Carolina at Chapel Hill · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · WASHINGTON UNIVERSITY · 2001 to 2025
$19.4M
Molecular Mechanisms of Castration Resistant Prostate Cancer Recurrence & Therapeutic StrategiesR01CA227025 · NCI · WASHINGTON UNIVERSITY · PI Felix Yi-Chung Feng, Nupam P Mahajan · 2021 to 2023
$1.8M
NCATS NIH HHS UL1 TR000448NCI NIH HHS P30 CA091842NCI NIH HHS R01 CA208258NCI NIH HHS R01 CA227025NIGMS NIH HHS P41 GM103422NIGMS NIH HHS R35 GM131731
6 · The paper itself

Abstract

The challenge of rapid macromolecular synthesis enforces the energy-hungry cancer cell mitochondria to switch their metabolic phenotypes, accomplished by activation of oncogenic tyrosine kinases. Precisely how kinase activity is directly exploited by cancer cell mitochondria to meet high-energy demand, remains to be deciphered. Here we show that a non-receptor tyrosine kinase, TNK2/ACK1 (tyrosine kinase non receptor 2), phosphorylated ATP5F1A (ATP synthase F1 subunit alpha) at Tyr243 and Tyr246 (Tyr200 and 203 in the mature protein, respectively) that not only increased the stability of complex V, but also increased mitochondrial energy output in cancer cells. Further, phospho-ATP5F1A (p-Y-ATP5F1A) prevented its binding to its physiological inhibitor, ATP5IF1 (ATP synthase inhibitory factor subunit 1), causing sustained mitochondrial activity to promote cancer cell growth. TNK2 inhibitor, (

Indexed as

AutophagyProstatic NeoplasmsAdenosine TriphosphateAnimalsHumansMaleMiceMice, TransgenicMitochondriaPhosphorylationProtein-Tyrosine KinasesQuinazolinonesTyrosine3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinoneAdenosine TriphosphateProtein-Tyrosine KinasesQuinazolinonesTNK2 protein, humanTyrosineATP5F1AATP5IF1mitochondrial dysfunctionmitochondrial vulnerabilitymitophagyTNK2/ACK1tyrosine phosphorylation

Identifiers

PMID35895804
PMCPMC9980697
OpenAlexW4288051710

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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 Socratic graph.