Evidence map›Paper›PMID 37443843›Full record

ArticleCells2023

Tissue Inhibitor of Metalloproteinases-1 Overexpression Mediates Chemoresistance in Triple-Negative Breast Cancer Cells.

Lisa Agnello, Annachiara d'Argenio, Alessandra Caliendo, Roberto Nilo, Antonella Zannetti, Monica Fedele, Simona Camorani, Laura Cerchia

Open access · goldAbstract read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

9 citing papers in PubMed, 16 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

8 authors at 2 institutions in 1 country.

Lisa AgnelloInstitute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council (CNR), 80131 Naples, Italy.ORCID 0000-0001-5923-1987
Annachiara d'ArgenioInstitute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council (CNR), 80131 Naples, Italy.
Alessandra CaliendoInstitute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council (CNR), 80131 Naples, Italy.ORCID 0009-0001-2506-513X
Roberto NiloInstitute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council (CNR), 80131 Naples, Italy.
Antonella ZannettiInstitute of Biostructures and Bioimaging, National Research Council (CNR), 80145 Naples, Italy.ORCID 0000-0002-6753-3659
Monica FedeleInstitute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council (CNR), 80131 Naples, Italy.ORCID 0000-0002-9171-1312
Simona CamoraniInstitute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council (CNR), 80131 Naples, Italy.ORCID 0000-0003-1144-0485
Laura CerchiaInstitute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council (CNR), 80131 Naples, Italy.ORCID 0000-0002-7633-7932
Institute for Experimental Endocrinology and Oncology · ITInstitute of Biostructure and Bioimaging · IT

Funding

Fondazione Associazione Italiana per la Ricerca sul Cancro 23052
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is among the most aggressive breast cancer subtypes. Despite being initially responsive to chemotherapy, patients develop drug-resistant and metastatic tumors. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a secreted protein with a tumor suppressor function due to its anti-proteolytic activity. Nevertheless, evidence indicates that TIMP-1 binds to the CD63 receptor and activates noncanonical oncogenic signaling in several cancers, but its role in mediating TNBC chemoresistance is still largely unexplored. Here, we show that mesenchymal-like TNBC cells express TIMP-1, whose levels are further increased in cells generated to be resistant to cisplatin (Cis-Pt-R) and doxorubicin (Dox-R). Moreover, public dataset analyses indicate that high TIMP-1 levels are associated with a worse prognosis in TNBC subjected to chemotherapy. Knock-down of TIMP-1 in both Cis-Pt-R and Dox-R cells reverses their resistance by inhibiting AKT activation. Consistently, TNBC cells exposed to recombinant TIMP-1 or TIMP-1-enriched media from chemoresistant cells, acquire resistance to both cisplatin and doxorubicin. Importantly, released TIMP-1 reassociates with plasma membrane by binding to CD63 and, in the absence of CD63 expression, TIMP-1-mediated chemoresistance is blocked. Thus, our results identify TIMP-1 as a new biomarker of TNBC chemoresistance and lay the groundwork for evaluating whether blockade of TIMP-1 signal is a viable treatment strategy.

Indexed as

Triple Negative Breast NeoplasmsCisplatinDoxorubicinDrug Resistance, NeoplasmHumansTissue Inhibitor of Metalloproteinase-1CisplatinDoxorubicinTissue Inhibitor of Metalloproteinase-1CD63 cell receptorchemoresistancetissue inhibitor of metalloproteinases-1triple-negative breast cancertumor microenvironment

Identifiers

PMID37443843
PMCPMC10340747
OpenAlexW4383819681

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.