Evidence map›Paper›PMID 41002380›Full record

ArticleCells2025

TIMP-1 Modulation Correlates with KRAS Dependency and EMT Induction in NSCLC.

Ilamathi M-Thirusenthilarasan, Pankaj Ahluwalia, Nithyananda Thorenoor, Sampa Ghoshal-Gupta, Byung Rho Lee, Bilal Siddiqui, Ravindra Kolhe, Amyn M Rojiani, Mumtaz V Rojiani

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. KRAS G12C inhibitors in KRASFrontiers in immunology · 2026
    Pooled it
  2. 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

9 authors.

Ilamathi M-ThirusenthilarasanDepartment of Pathology, Penn State College of Medicine, Hershey, PA 17033, USA.ORCID 0000-0002-2825-8164
Pankaj AhluwaliaDepartment of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.ORCID 0000-0003-0060-6152
Nithyananda ThorenoorDepartment of Pathology, Penn State College of Medicine, Hershey, PA 17033, USA.ORCID 0000-0003-2958-4065
Sampa Ghoshal-GuptaDepartment of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Byung Rho LeeDepartment of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Bilal SiddiquiDepartment of Pathology, Penn State College of Medicine, Hershey, PA 17033, USA.
Ravindra KolheDepartment of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.ORCID 0000-0002-8283-2403
Amyn M RojianiDepartment of Pathology, Penn State College of Medicine, Hershey, PA 17033, USA.ORCID 0000-0001-5621-3724
Mumtaz V RojianiDepartment of Pathology, Penn State College of Medicine, Hershey, PA 17033, USA.ORCID 0000-0002-0597-9305

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated genes in human cancer, including non-small cell lung carcinoma (NSCLC). Sustained expression of KRAS is required for survival in KRAS-dependent tumors. KRAS tumors can become independent upon bypassing this addiction. Tissue inhibitor of metalloproteinase-1 (TIMP-1) exhibits a range of novel functions in addition to its initially recognized activity as a physiological inhibitor of matrix metalloproteinases (MMPs). It has repeatedly been associated with cancer progression and poor prognosis in multiple cancers. This study investigates the relationship between TIMP-1 modulation and KRAS dependency in NSCLC. We found an inverse expression of KRAS and TIMP-1 in NSCLC lines. Modulating TIMP-1 levels altered KRAS expression and affected KRAS-dependency features. Overexpression of TIMP-1 decreases the KRAS levels in dependent cells and knocking-down TIMP-1 increases KRAS levels in independent cells with concomitant change in RAS-GTP levels. TIMP-1 modulation influenced apoptosis upon KRAS ablation, with TIMP-1 overexpression decreasing apoptosis in dependent cells and TIMP-1 knockdown increasing it in independent cells. Bioinformatic analysis depicted variant-specific perturbations between KRAS and TIMP-1 expression. Furthermore, EMT marker expression was altered upon TIMP-1 modulation, suggesting the role of TIMP-1 in EMT induction in KRAS-independent cells. These findings emphasize the intricate relationship between TIMP-1 and KRAS in NSCLC, shedding light on potential mechanisms underlying tumor behavior and response to therapy.

Indexed as

Carcinoma, Non-Small-Cell LungEpithelial-Mesenchymal TransitionLung NeoplasmsProto-Oncogene Proteins p21(ras)Tissue Inhibitor of Metalloproteinase-1ApoptosisCell Line, TumorGene Expression Regulation, NeoplasticHumansKRAS protein, humanProto-Oncogene Proteins p21(ras)TIMP1 protein, humanTissue Inhibitor of Metalloproteinase-1epithelial–mesenchymal transitionKRASnon-small cell lung carcinomaoncogene addictionTIMP-1

Identifiers

PMID41002380
PMCPMC12468282

What OpenQuestion holds

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Registered trials

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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.