NDLI: Emerging role of IGF1R and IR expression and localisation in adrenocortical carcinomas

Content Provider	Springer Nature : BioMed Central
Author	Catalano, Rosa Nozza, Emma Altieri, Barbara Esposito, Emanuela Croci, Giorgio A. Barbieri, Anna Maria Treppiedi, Donatella Di Bari, Sonia Kimpel, Otilia Detomas, Mario Tamburello, Mariangela Schauer, Marc P. Herterich, Sabine Angelousi, Anna Luconi, Michaela Canu, Letizia Nesi, Gabriella Hantel, Constanze Sigala, Sandra Landwehr, Laura-Sophie Di Dalmazi, Guido Cassinotti, Elisa Baldari, Ludovica Palmieri, Serena Mangone, Alessandra Ferrante, Emanuele Ronchi, Cristina L. Mantovani, Giovanna Peverelli, Erika
Abstract	Background The insulin-like growth factor 2 (IGF2) is overexpressed in 90% of adrenocortical carcinomas (ACC) and promotes cell proliferation via IGF1R and isoform A of insulin receptor (IRA). However, IGF2 role in ACC tumourigenesis has not been completely understood yet, and the contribution of IGF1R and IRA in mediating ACC cell growth has been poorly explored. This study aimed to investigate IGF1R and IR expression and localisation, including the expression of IR isoforms, in ACC and adrenocortical adenomas (ACA), and their role in IGF2-driven proliferation. Methods Immunohistochemistry staining of IGF1R and IR was performed on 118 ACC and 22 ACA to evaluate their expression and cellular localisation and statistical analyses were carried out to assess correlations with clinicopathological data. The expression of IRA and IRB in ACC and ACA tissues, ACC cell lines and ACC and ACA primary cultures was determined by RT-qPCR. To appraise the specific role of IGF1R and IR in mediating IGF2 mitogenic pathway, single and double silencing of receptors and their inhibition in 2 ACC cell lines derived from primary tumours (H295R and JIL-2266) and 2 derived from metastatic tumours (MUC-1 and TVBF-7) as well as in ACC and ACA primary cultures were performed. Results We found a higher IGF1R plasma membrane localisation in ACC compared to ACA. In ACC this localisation was associated with higher Ki67 and Weiss score. IR was expressed in about half of ACC and in all ACA but, in ACC, it was associated with higher Ki67 and Weiss score. RT-qPCR revealed that the prevalent isoform of IR was IRA in ACC and ACA, but not in normal adrenals. In ACC cell lines, double IGF1R + IR silencing reduced cell proliferation in JIL-2266, MUC-1 and TVBF-7 but not in H295R. In ACC, but not ACA, primary cultures, cell proliferation was reduced after IR but not IGF1R knockdown. Conclusions Overall, these data suggest that IGF1R localisation and IR expression represent new biomarkers predicting tumour aggressiveness, as well as possible molecular markers useful to patients’ stratification for more individualized IGF1R-IR targeted therapies or for novel pharmacological approaches specifically targeting IRA isoform.
Related Links	https://biosignaling.biomedcentral.com/counter/pdf/10.1186/s12964-025-02115-0.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12964-025-02115-0
Journal	Cell Communication and Signaling
Issue Number	1
Volume Number	23
Language	English
Publisher	BioMed Central
Publisher Date	2025-03-04
Access Restriction	Open
Subject Keyword	Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors Adrenocortical carcinoma IGF1R Insulin receptor Biomarker Cellular localisation
Content Type	Text
Resource Type	Article
Subject	Biochemistry Cell Biology Molecular Biology
Journal Impact Factor	8.2/2023
5-Year Journal Impact Factor	8/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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