Evidence map›Paper›PMID 28368412›Full record

ArticleOncogene2017

Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma.

A Po, M Silvano, E Miele, C Capalbo, A Eramo, V Salvati, M Todaro, Z M Besharat, G Catanzaro, D Cucchi and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
4.8field-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.

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

66 citing papers in PubMed, 115 citations in OpenAlex.

  1. Article
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  3. [Molecular cancer · 2026
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  7. Cell signaling inFrontiers in cellular and infection microbiology · 2025
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  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. The lung mesenchyme in development, regeneration, and fibrosis.The Journal of clinical investigation · 2023
    Review
  17. Article
  18. Article
  19. Article
  20. [SOX2-OT/SOX2 axis regulates lung cancer H520 cell migrationNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022
    Article

6 more citing papers are in PubMed but not listed here.

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

20 authors at 6 institutions in 1 country.

A PoDepartment of Molecular Medicine, Sapienza University, Rome, Italy.
M SilvanoDepartment of Molecular Medicine, Sapienza University, Rome, Italy.
E MieleCenter for Life NanoScience@Sapienza, IIT, Rome, Italy.
C CapalboDepartment of Molecular Medicine, Sapienza University, Rome, Italy.
A EramoDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
V SalvatiDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
M TodaroSurgical and Oncological Sciences, University of Palermo, Palermo, Italy.
Z M BesharatDepartment of Molecular Medicine, Sapienza University, Rome, Italy.
G CatanzaroDepartment of Experimental Medicine, Sapienza University, Rome, Italy.
D CucchiDepartment of Molecular Medicine, Sapienza University, Rome, Italy.
S ConiDepartment of Molecular Medicine, Sapienza University, Rome, Italy.
L Di MarcotullioDepartment of Molecular Medicine, Sapienza University, Rome, Italy.
G CanettieriDepartment of Molecular Medicine, Sapienza University, Rome, Italy.
A VaccaDepartment of Experimental Medicine, Sapienza University, Rome, Italy.
G StassiSurgical and Oncological Sciences, University of Palermo, Palermo, Italy.
E De SmaeleDepartment of Experimental Medicine, Sapienza University, Rome, Italy.
M TartagliaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
I ScrepantiDepartment of Molecular Medicine, Sapienza University, Rome, Italy.
R De MariaDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
E FerrettiDepartment of Experimental Medicine, Sapienza University, Rome, Italy.
Sapienza University of Rome · ITCenter for Nano Science and Technology · ITIstituto Superiore di Sanità · ITUniversity of Palermo · ITBambino Gesù Children's Hospital · ITUniversità Cattolica del Sacro Cuore · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. We show that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. In LAC cells including the cancer stem cell compartment, we show that GLI1 is activated noncanonically by MAPK/ERK signaling. Different mechanisms can trigger the MAPK/ERK/GLI1 cascade including KRAS mutation and stimulation of NRP2 by VEGF produced by the cancer cells themselves in an autocrine loop or by stromal cells as paracrine cross talk. Suppression of GLI1, by silencing or drug-mediated, inhibits LAC cells proliferation, attenuates their stemness and increases their susceptibility to apoptosis in vitro and in vivo. These findings provide insight into the growth of LACs and point to GLI1 as a downstream effector for oncogenic pathways. Thus, strategies involving direct inhibition of GLI1 may be useful in the treatment of LACs.

Indexed as

AdenocarcinomaAnimalsCarcinoma, Non-Small-Cell LungCell Line, TumorFemaleHumansLung NeoplasmsMiceMice, SCIDMitogen-Activated Protein Kinase KinasesNeoplastic Stem CellsNeuropilin-2Proto-Oncogene Proteins p21(ras)PyridinesPyrimidinesRNA InterferenceGANT 61Hras protein, mouseKRAS protein, humanMitogen-Activated Protein Kinase KinasesNeuropilin-2Proto-Oncogene Proteins p21(ras)PyridinesPyrimidinesRNA, Small InterferingZinc Finger Protein GLI1

Identifiers

PMID28368412
PMCPMC5558095
OpenAlexW2605225604

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.