Studies on insulin-like growth factor 1 receptor (IGF-1R) and its role in malignant cell growth – Olle Larsson's Group

Studies on insulin-like growth factor 1 receptor (IGF-1R) and its role in malignant cell growth. IGF-1R is critical for malignant cell growth but is not an absolute requirement for normal cells. Our research attempts to identify mechanisms responsible for the critical roles of IGF-1R in cancer as well as to develop selective anti-IGF-1R agents for tumor treatment.

Our research

The insulin-like growth factor 1 receptor (IGF-1R) is an evolutionarily very ancient receptor tyrosine kinase (RTK). IGF-1R is a heterotetramer consisting of two ligand-binding extracellular alpha-subunits and two beta-subunits composing of a transmembrane domain, an intracellular tyrosine kinase domain, and a C-terminal tail. Ligand (IGF-1 or IGF-2) binding induces tyrosines within the TK domain to be trans-phosphorylated by the dimeric subunit partner.

During the last 15 years it has becoming increasingly evident that the IGF-1R is crucial for tumor transformation, cancer cell growth, tumor progression, and therapy resistance. IGF-1R is expressed in almost all types of malignancies and generally the receptor levels are substantially higher in cancer compared to normal tissues. Accordingly, IGF-1R is currently being one of the most promising targets for modern cancer treatment.

The mechanisms underlying the fundamental roles of IGF-1R in cancer biology are still not well understood. Actually, IGF-1R shares the major signaling pathways with many RTKs, like the insulin receptor isoform B (IR-B) which is not important for tumor growth. Probably, IGF-1R promotes alternative IGF-1R signaling and actions in cancer cells. Since several years ago we have sought to disclose novel and alternative IGF-1R mechanisms with relevance to cancer cell growth. We have e.g. demonstrated ubiquitination of the receptor and that this modification promotes MAPK/ERK signaling and cell cycle progression, and we have identified two involved E3-ligases (enzymes catalysing ubiquitination) with distinct mode of actions.

Our recent finding that IGF-1R undergoes SUMOylation, leading to its nuclear accumulation and gene activation by binding to enhancer regions, constitutes a novel and alternative regulatory mechanism for the receptor. The SUMOylation sites of IGF-1R were identified as three evolutionarily conserved lysine residuesLys1025, Lys1100, and Lys1120in the b-subunit of the receptor. If these SUMO sites were mutated the IGF-1R could not accumulate in the cell nucleus and enhance transcription. The whole receptor, the heterotetramer, was shown to undergo SUMO-dependent translocation to the cell nucleus. Our findings represent a breakthrough in IGF-1R research and have potentially wide implications for cell signaling.

Our current research focuses on role of nuclear IGF-1R in the cancer cell. The long-term aims are to develop improved diagnostic and therapeutic tools using IGF-1R as a target.


Selected publications

Staff and contact

Group leader

All members of the group


Ahmed Waraky
Insulin-like growth factor 1 receptor, novel functions and future possibilities
22 september 2017

Sylvia Packham
From membrane to nucleus: new roles and functions of SUMOylated IGF-1R and EGFR
17 april 2015

Dudi Warsito
The secret life of nuclear IGF-1R: functions beyond traditional signaling pathways
24 oktober 2014

Natalia Natalishvili
IGF-1R: Studies on the expression and role in transformation
29 maj 2009

Sandra Andersson
The many faces of IGF-1R from cell surface to the nucleus
22 maj 2009

Linda Rosengren
Targeting the GH/IGF-1 axis with novel, small molecule inhibitors.
26 oktober 2007

Bita Sehat
SUMO and ubiquitin : The Yin and Yang of IGF-1R function
25 oktober 2007

Mario A Economou
Uveal melanoma and macular degeneration : Molecular biology and potential therapeutic applications
September 7, 2007

Radu Vasilcanu
Regulation of insulin-like growth factor-1 receptor expression and signaling.
June 15, 2007

Daiana Vasilcanu
IGF-1R inhibition : A tool for functional studies of insulin-like growth factor family in malignant cells.
February 3, 2006

Ada Girnita
Targeting insulin-like growth factor-1 receptor in cancer
October 15, 2004

Maria Törnkvist
Synovial sarcoma : molecular, biological and clinical implications
September 3, 2004

Leonard Girnita
Growth factor pathways in human cancer : Functional and therapeutic implications.
October 25, 2002

Charlotta All-Ericsson
Uveal melanoma : Cytogenetics, molecular biology and tumor immunology.
October 4, 2002

Yuntao Xie
The biological role and clinical impact of SYT-SSX fusion gene and IGF-1R in synovial sarcoma
June 12, 2002