Insulin-like growth factors are essential to prevent anoikis in oestrogen-responsive breast cancer cells: importance of the type I IGF receptor and PI3-kinase/Akt pathway

Molecular Cancer
Brendan C Luey, Felicity E B May

Abstract

Detachment of epithelial cells from the extracellular matrix initiates programmed cell death by a process termed anoikis. Malignant cells must acquire anoikis resistance to leave the primary tumour and metastasise. Multiple signal transduction pathways can activate anoikis and confer anoikis resistance, but these are not understood in breast cancer. Models for anoikis of oestrogen-responsive breast cancer cells were established and the protective effects of IGF-1 tested. Cleaved PARP was measured by western transfer and cleaved caspase 3 by flow cytometry. Pathways involved in anoikis and in anoikis resistance were investigated with PI3-kinase, Akt, and MEK1 and MEK2 inhibitors. The importance of the type I IGF receptor was investigated by IGF-concentration dependence, siRNA knockdown and pharmacological inhibition. Association between IGF-1R expression and relapse with distant metastasis was analysed in 1609 patients by log rank test. Unattached breast cancer cells required culture in serum-free medium to induce anoikis. Rapid loss of FAK, Akt and Bad phosphorylation was concurrent with anoiks induction, but ERK1 and ERK2 phosphorylation increased which suggested that anoikis resistance is mediated by the PI3-kinase/Akt rather...Continue Reading

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Citations

Jun 24, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jia LiuZhong-Hou Han
Dec 1, 2017·International Journal of Molecular Sciences·Marilina García-Aranda, Maximino Redondo
Aug 15, 2018·Journal of Cellular Physiology·Hojjat Naderi-Meshkin, Naghmeh Ahmadiankia
Sep 15, 2018·Endocrinology·Chifei KangEmily J Gallagher
Feb 11, 2021·Cancers·Damiano Cosimo RigiraccioloRosamaria Lappano
Jan 23, 2021·Biomolecules·Federica BielloAlessandra Gennari
Dec 15, 2020·World Journal of Stem Cells·Gretel Mendoza-AlmanzaJorge Olmos
Apr 16, 2021·Frontiers in Oncology·Funmilayo O AdeshakinXiaochun Wan
Jun 18, 2021·Frontiers in Pharmacology·Hongdan HeHengxiu Yan

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Methods Mentioned

BETA
transgenic
X-ray
flow cytometry
transfection
electrophoresis

Software Mentioned

WinMDI
Labworks

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