Evidence map›Paper›PMID 25391374›Full record

ArticleMolecular pharmacology2015

Insulin-like growth factor-1 receptor signaling increases the invasive potential of human epidermal growth factor receptor 2-overexpressing breast cancer cells via Src-focal adhesion kinase and forkhead box protein M1.

Eduardo Sanabria-Figueroa, Siobhan M Donnelly, Kevin C Foy, Meghan C Buss, Robert C Castellino, Elisavet Paplomata, Latonia Taliaferro-Smith, Pravin T P Kaumaya, Rita Nahta

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

32 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
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  4. Review
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  6. Virus-like Particle (VLP) Vaccines for Cancer Immunotherapy.International journal of molecular sciences · 2023
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  9. Recent advances and limitations in the application of kahalalides for the control of cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022
    Review
  10. Review
  11. Review
  12. Article
  13. Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer.Frontiers in cell and developmental biology · 2021
    Review
  14. Article
  15. Review
  16. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Eduardo Sanabria-FigueroaDepartments of Pharmacology (E.S.-F., S.M.D., R.N.) and Hematology and Medical Oncology (E.P., L.T.-S., R.N.), School of Medicine, and Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences (E.S.-F., R.N.), and Winship Cancer Institute (R.C.C., E.P., L.T.-S., R.N.), Emory University, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (M.C.B., R.C.C.); and Departments of Obstetrics and Gynecology and Microbiology, James Cancer Hospital, Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio (K.C.F., P.T.P.K.).
Siobhan M DonnellyDepartments of Pharmacology (E.S.-F., S.M.D., R.N.) and Hematology and Medical Oncology (E.P., L.T.-S., R.N.), School of Medicine, and Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences (E.S.-F., R.N.), and Winship Cancer Institute (R.C.C., E.P., L.T.-S., R.N.), Emory University, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (M.C.B., R.C.C.); and Departments of Obstetrics and Gynecology and Microbiology, James Cancer Hospital, Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio (K.C.F., P.T.P.K.).
Kevin C FoyDepartments of Pharmacology (E.S.-F., S.M.D., R.N.) and Hematology and Medical Oncology (E.P., L.T.-S., R.N.), School of Medicine, and Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences (E.S.-F., R.N.), and Winship Cancer Institute (R.C.C., E.P., L.T.-S., R.N.), Emory University, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (M.C.B., R.C.C.); and Departments of Obstetrics and Gynecology and Microbiology, James Cancer Hospital, Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio (K.C.F., P.T.P.K.).
Meghan C BussDepartments of Pharmacology (E.S.-F., S.M.D., R.N.) and Hematology and Medical Oncology (E.P., L.T.-S., R.N.), School of Medicine, and Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences (E.S.-F., R.N.), and Winship Cancer Institute (R.C.C., E.P., L.T.-S., R.N.), Emory University, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (M.C.B., R.C.C.); and Departments of Obstetrics and Gynecology and Microbiology, James Cancer Hospital, Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio (K.C.F., P.T.P.K.).
Robert C CastellinoDepartments of Pharmacology (E.S.-F., S.M.D., R.N.) and Hematology and Medical Oncology (E.P., L.T.-S., R.N.), School of Medicine, and Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences (E.S.-F., R.N.), and Winship Cancer Institute (R.C.C., E.P., L.T.-S., R.N.), Emory University, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (M.C.B., R.C.C.); and Departments of Obstetrics and Gynecology and Microbiology, James Cancer Hospital, Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio (K.C.F., P.T.P.K.).
Elisavet PaplomataDepartments of Pharmacology (E.S.-F., S.M.D., R.N.) and Hematology and Medical Oncology (E.P., L.T.-S., R.N.), School of Medicine, and Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences (E.S.-F., R.N.), and Winship Cancer Institute (R.C.C., E.P., L.T.-S., R.N.), Emory University, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (M.C.B., R.C.C.); and Departments of Obstetrics and Gynecology and Microbiology, James Cancer Hospital, Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio (K.C.F., P.T.P.K.).
Latonia Taliaferro-SmithDepartments of Pharmacology (E.S.-F., S.M.D., R.N.) and Hematology and Medical Oncology (E.P., L.T.-S., R.N.), School of Medicine, and Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences (E.S.-F., R.N.), and Winship Cancer Institute (R.C.C., E.P., L.T.-S., R.N.), Emory University, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (M.C.B., R.C.C.); and Departments of Obstetrics and Gynecology and Microbiology, James Cancer Hospital, Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio (K.C.F., P.T.P.K.).
Pravin T P KaumayaDepartments of Pharmacology (E.S.-F., S.M.D., R.N.) and Hematology and Medical Oncology (E.P., L.T.-S., R.N.), School of Medicine, and Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences (E.S.-F., R.N.), and Winship Cancer Institute (R.C.C., E.P., L.T.-S., R.N.), Emory University, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (M.C.B., R.C.C.); and Departments of Obstetrics and Gynecology and Microbiology, James Cancer Hospital, Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio (K.C.F., P.T.P.K.).
Rita NahtaDepartments of Pharmacology (E.S.-F., S.M.D., R.N.) and Hematology and Medical Oncology (E.P., L.T.-S., R.N.), School of Medicine, and Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences (E.S.-F., R.N.), and Winship Cancer Institute (R.C.C., E.P., L.T.-S., R.N.), Emory University, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (M.C.B., R.C.C.); and Departments of Obstetrics and Gynecology and Microbiology, James Cancer Hospital, Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio (K.C.F., P.T.P.K.) rnahta@emory.edu.
Children's Healthcare of Atlanta · USThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USWinship Cancer Institute

Funding

Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Suresh S Ramalingam · 2009 to 2026
$47.5M
Graduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1M
Mechanisms of Herceptin resistanceR01CA157754 · NCI · EMORY UNIVERSITY · PI NAHTA, RITA · 2012 to 2016
$1.8M
NCI NIH HHS P30 CA138292NCI NIH HHS P30CA138292NCI NIH HHS R01 CA157754NCI NIH HHS R01CA157754NIGMS NIH HHS T32 GM008602
6 · The paper itself

Abstract

Resistance to the human epidermal growth factor receptor (HER2)-targeted antibody trastuzumab is a major clinical concern in the treatment of HER2-positive metastatic breast cancer. Increased expression or signaling from the insulin-like growth factor-1 receptor (IGF-1R) has been reported to be associated with trastuzumab resistance. However, the specific molecular and biologic mechanisms through which IGF-1R promotes resistance or disease progression remain poorly defined. In this study, we found that the major biologic effect promoted by IGF-1R was invasion, which was mediated by both Src-focal adhesion kinase (FAK) signaling and Forkhead box protein M1 (FoxM1). Cotargeting IGF-1R and HER2 using either IGF-1R antibodies or IGF-1R short hairpin RNA in combination with trastuzumab resulted in significant but modest growth inhibition. Reduced invasion was the most significant biologic effect achieved by cotargeting IGF-1R and HER2 in trastuzumab-resistant cells. Constitutively active Src blocked the anti-invasive effect of IGF-1R/HER2 cotargeted therapy. Furthermore, knockdown of FoxM1 blocked IGF-1-mediated invasion, and dual targeting of IGF-1R and HER2 reduced expression of FoxM1. Re-expression of FoxM1 restored the invasive potential of IGF-1R knockdown cells treated with trastuzumab. Overall, our results strongly indicate that therapeutic combinations that cotarget IGF-1R and HER2 may reduce the invasive potential of cancer cells that are resistant to trastuzumab through mechanisms that depend in part on Src and FoxM1.

Indexed as

Gene Expression Regulation, NeoplasticBreast NeoplasmsCell Line, TumorErb-b2 Receptor Tyrosine KinasesFemaleFocal Adhesion Kinase 1Forkhead Box Protein M1Forkhead Transcription FactorsGenes, srcHumansReceptor, IGF Type 1RNA, Small InterferingSignal TransductionERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesFocal Adhesion Kinase 1Forkhead Box Protein M1Forkhead Transcription FactorsFOXM1 protein, humanPTK2 protein, humanReceptor, IGF Type 1RNA, Small Interfering

Identifiers

PMID25391374
PMCPMC4293451
OpenAlexW2151274388

What OpenQuestion holds

Textmetadata
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.