Evidence map›Paper›PMID 22728436›Full record

ArticleCancer discovery2012

A bioluminescent transposon reporter-trap identifies tumor-specific microenvironment-induced promoters in Salmonella for conditional bacterial-based tumor therapy.

Kelly Flentie, Brandon Kocher, Seth T Gammon, Deborah V Novack, Jeffrey S McKinney, David Piwnica-Worms

Open access · greenAbstract read
In one paragraph

Article in Cancer discovery, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

37 citing papers in PubMed, 87 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Microbial Biotechnology in Medicine.Progress in molecular and subcellular biology · 2026
    Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Current advances in microbial-based cancer therapies.Medical oncology (Northwood, London, England) · 2023
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Frontiers in cellular and infection microbiology · 2023
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Kelly FlentieBRIGHT Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Brandon Kocher
Seth T Gammon
Deborah V Novack
Jeffrey S McKinney
David Piwnica-Worms
Mallinckrodt (United States) · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
WU-MDACC Inter-Institutional Molecular Imaging CenterP50CA094056 · NCI · WASHINGTON UNIVERSITY · PI KOPAN, RAPHAEL · 2002 to 2016
$26.3M
TRAINING PROGRAM IN CELLULAR AND MOLECULAR BIOLOGYT32GM007067 · NIGMS · WASHINGTON UNIVERSITY · PI TRUE-KROB, HEATHER L · 1985 to 2020
$20.4M
MOLECULAR ONCOLOGY TRAINING GRANTT32CA113275 · NCI · WASHINGTON UNIVERSITY · PI Matthew J Walter · 2006 to 2026
$5.7M
NF-kB SUBUNITS p65 AND RelB IN OSTEOCLASTSR01AR052705 · NIAMS · WASHINGTON UNIVERSITY · PI VEIS, DEBORAH J · 2006 to 2015
$3.0M
NCI NIH HHS P30 CA091842NCI NIH HHS P30 CA91842NCI NIH HHS P50 CA094056NCI NIH HHS P50 CA94056NCI NIH HHS T32 CA113275NIAMS NIH HHS R01 AR052705NIGMS NIH HHS T32 GM007067
6 · The paper itself

Abstract

unlabelledSalmonella specifically localize to malignant tumors in vivo, a trait potentially exploitable as a delivery system for cancer therapeutics. To characterize mechanisms and genetic responses of Salmonella during interaction with living neoplastic cells, we custom-designed a promoterless transposon reporter containing bacterial luciferase. Analysis of a library containing 7,400 independent Salmonella transposon insertion mutants in coculture with melanoma or colon carcinoma cells identified five bacterial genes specifically activated by cancer cells: adiY, yohJ, STM1787, STM1791, and STM1793. Experiments linked acidic pH, a common characteristic of the tumor microenvironment, to a strong, specific, and reversible stimulus for activation of these Salmonella genes in vitro and in vivo. Indeed, a Salmonella reporter strain encoding a luciferase transgene regulated by the STM1787 promoter, which contains a tusp motif, showed tumor-induced bioluminescence in vivo. Furthermore, Salmonella expressing Shiga toxin from the STM1787 promoter provided potent and selective antitumor activity in vitro and in vivo, showing the potential for a conditional bacterial-based tumor-specific therapeutic. SIGNIFICANCE: Salmonella, which often encounter acidic environments during classical host infection, may co-opt evolutionarily conserved pathways for tumor colonization in response to the acidic tumor microenvironment. We identified specific promoter sequences that provide a platform for targeted Salmonella-based tumor therapy in vivo.

Indexed as

AnimalsCell Line, TumorDNA Transposable ElementsGene ExpressionGenes, BacterialGenetic TherapyGene Transfer TechniquesHCT116 CellsHeLa CellsHumansLuciferasesLuminescent MeasurementsMiceMice, NudeNeoplasmsPromoter Regions, GeneticDNA Transposable ElementsLuciferases

Identifiers

PMID22728436
PMCPMC3395769
OpenAlexW2134412946

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.