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Ret Receptor Has Distinct Alterations and Functions in Breast Cancer

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Ret receptor tyrosine kinase is a proto-oncogene that participates in development of various cancers. Several independent studies have recently identified Ret as a key player in breast cancer. Although Ret overexpression and function have been under investigation, mainly in estrogen receptor positive breast cancer, a more comprehensive analysis of the impact of recurring Ret alterations in breast cancer is needed. This review consolidates the current knowledge of Ret alterations and their potential effects in breast cancer. We discuss and integrate data on Ret changes in different breast cancer subtypes and potential function in progression, as well as the participation of distinct Ret network signaling partners in these processes. We propose that it will be essential to define a shared molecular feature of tumors with alteration in Ret receptor, be this at the genetic level or via overexpression in order to design effective therapies to target the Ret pathway. Here we review experimental evidence from basic research and pre-clinical studies concentrating on Ret alterations as potential biomarkers for recurrence, and we discuss the possibility that targeting the Ret pathway might in the future become a treatment for breast cancer.

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Abbreviations

ARTN:

artemin

COSMIC:

Catalogue of Somatic Mutations In Cancer

E2 :

estrogen

ER :

estrogen receptor

ERE:

estrogen response element

GDNF:

glial-derived neurotrophic factor

GFL:

glial-derived neurotrophic factor family ligand

GFRa:

GDNF family a co-receptor

NRTN:

neurturin

NSCLC:

non-small cell lung adenocarcinoma

PDX:

patient derived xenograft

PR:

progesterone receptor

PRSN:

presephin

Ret:

REarragement during Transfection

RTK:

receptor tyrosine kinase

TCGA:

The Cancer Genome Atlas

TK:

tyrosine kinase

TN:

triple negative

WT:

wild type

Y:

tyrosine residue

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Acknowledgements

This work was supported by the Argentinian grants, GFN°02 from Fundación para el progreso de la medicina (fpm), PICT-2016-2834 and PICT-2017-1268 from Agencia Nacional de Producción Científica y Tecnológica (ANPCyT), awarded to AG. SAV is supported by a scholarship from National Argentinian Research Council CONICET.

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Authors and Affiliations

  1. CONICET-UBA, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Ciudad Universitaria, C1428EGA CABA, Buenos Aires, Argentina

    Albana Gattelli, Ignacio E. Schor & Sabrina A. Vallone

  2. Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales, Ciudad Universitaria C1428EGA CABA, Buenos Aires, Argentina

    Albana Gattelli & Sabrina A. Vallone

  3. Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, CH-4058, Basel, Switzerland

    Nancy E. Hynes

  4. University of Basel, CH-4002, Basel, Switzerland

    Nancy E. Hynes

  5. Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Ciudad Universitaria, C1428EGA, CABA, Argentina

    Ignacio E. Schor

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  1. Albana Gattelli
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AG and NEH wrote and prepared the manuscript. IS performed the in silico analysis of publically available data. SAV contributed with the figures conception and preparation.

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Correspondence to Albana Gattelli.

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Gattelli, A., Hynes, N.E., Schor, I.E. et al. Ret Receptor Has Distinct Alterations and Functions in Breast Cancer. J Mammary Gland Biol Neoplasia 25, 13–26 (2020). https://doi.org/10.1007/s10911-020-09445-4

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