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Review

Below the Surface: IGF-1R Therapeutic Targeting and Its Endocytic Journey

by
Caitrin Crudden
1,2,
Dawei Song
1,
Sonia Cismas
1,
Eric Trocmé
1,3,
Sylvya Pasca
1,
George A. Calin
4,5,
Ada Girnita
1,6 and
Leonard Girnita
1,*
1
Department of Oncology-Pathology, Cellular and Molecular Tumor Pathology, Karolinska Institute, and Karolinska University Hospital, 17164 Stockholm, Sweden
2
Department of Pathology, Cancer Centre Amsterdam, Amsterdam UMC, VU University Medical Centre, 1081 HZ Amsterdam, The Netherlands
3
St. Erik Eye Hospital, 11282 Stockholm, Sweden
4
Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
5
Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
6
Dermatology Department, Karolinska University Hospital, 17176 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Cells 2019, 8(10), 1223; https://doi.org/10.3390/cells8101223
Submission received: 12 September 2019 / Revised: 30 September 2019 / Accepted: 3 October 2019 / Published: 9 October 2019
(This article belongs to the Special Issue Emerging Paradigms of Insulin-Like Activities: From Pathophysiology to Targeted Therapy in Cancer and Diabetes)
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Abstract

Ligand-activated plasma membrane receptors follow pathways of endocytosis through the endosomal sorting apparatus. Receptors cluster in clathrin-coated pits that bud inwards and enter the cell as clathrin-coated vesicles. These vesicles travel through the acidic endosome whereby receptors and ligands are sorted to be either recycled or degraded. The traditional paradigm postulated that the endocytosis role lay in signal termination through the removal of the receptor from the cell surface. It is now becoming clear that the internalization process governs more than receptor signal cessation and instead reigns over the entire spatial and temporal wiring of receptor signaling. Governing the localization, the post-translational modifications, and the scaffolding of receptors and downstream signal components established the endosomal platform as the master regulator of receptor function. Confinement of components within or between distinct organelles means that the endosome instructs the cell on how to interpret and translate the signal emanating from any given receptor complex into biological effects. This review explores this emerging paradigm with respect to the cancer-relevant insulin-like growth factor type 1 receptor (IGF-1R) and discusses how this perspective could inform future targeting strategies.
Keywords: insulin-like growth factor type 1 receptor; insulin receptor; RTK; GPCR; internalization; endocytosis; endosome; biased signaling; ubiquitination; β-arrestin insulin-like growth factor type 1 receptor; insulin receptor; RTK; GPCR; internalization; endocytosis; endosome; biased signaling; ubiquitination; β-arrestin

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MDPI and ACS Style

Crudden, C.; Song, D.; Cismas, S.; Trocmé, E.; Pasca, S.; Calin, G.A.; Girnita, A.; Girnita, L. Below the Surface: IGF-1R Therapeutic Targeting and Its Endocytic Journey. Cells 2019, 8, 1223. https://doi.org/10.3390/cells8101223

AMA Style

Crudden C, Song D, Cismas S, Trocmé E, Pasca S, Calin GA, Girnita A, Girnita L. Below the Surface: IGF-1R Therapeutic Targeting and Its Endocytic Journey. Cells. 2019; 8(10):1223. https://doi.org/10.3390/cells8101223

Chicago/Turabian Style

Crudden, Caitrin, Dawei Song, Sonia Cismas, Eric Trocmé, Sylvya Pasca, George A. Calin, Ada Girnita, and Leonard Girnita. 2019. "Below the Surface: IGF-1R Therapeutic Targeting and Its Endocytic Journey" Cells 8, no. 10: 1223. https://doi.org/10.3390/cells8101223

APA Style

Crudden, C., Song, D., Cismas, S., Trocmé, E., Pasca, S., Calin, G. A., Girnita, A., & Girnita, L. (2019). Below the Surface: IGF-1R Therapeutic Targeting and Its Endocytic Journey. Cells, 8(10), 1223. https://doi.org/10.3390/cells8101223

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