Insulin Enhances Migration and Invasion in Prostate Cancer Cells by Up-Regulation of FOXC2

Frontiers in Endocrinology
Phoebe L SarkarColleen Nelson

Abstract

Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer (PCa), yet many patients relapse with lethal metastatic disease. With this loss of androgens, increased cell plasticity has been observed as an adaptive response to ADT. This includes gain of invasive and migratory capabilities, which may contribute to PCa metastasis. Hyperinsulinemia, which develops as a side-effect of ADT, has been associated with increased tumor aggressiveness and faster treatment failure. We investigated the direct effects of insulin in PCa cells that may contribute to this progression. We measured cell migration and invasion induced by insulin using wound healing and transwell assays in a range of PCa cell lines of variable androgen dependency (LNCaP, 22RV1, DuCaP, and DU145 cell lines). To determine the molecular events driving insulin-induced invasion we used transcriptomics, quantitative real time-PCR, and immunoblotting in three PCa cell lines. Insulin increased invasiveness of PCa cells, upregulating Forkhead Box Protein C2 (FOXC2), and activating key PCa cell plasticity mechanisms including gene changes consistent with epithelial-to-mesenchymal transition (EMT) and a neuroendocrine phenotype. Additionally, analy...Continue Reading

References

Jun 17, 2004·American Journal of Physiology. Endocrinology and Metabolism·Gina B Di GregorioPhilip A Kern
Jul 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Yan Ping YuJian-Hua Luo
Oct 26, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jan Hammarsten, Benkt Högstedt
Apr 28, 2006·Nature Genetics·Michael ReichJill P Mesirov
Sep 5, 2006·Cancer Research·Jason J Christiansen, Ayyappan K Rajasekaran
Aug 30, 2007·The Journal of Clinical Endocrinology and Metabolism·Maria A YialamasFrances J Hayes
Sep 12, 2008·The Prostate·Michael E CoxMichael Pollak
Dec 10, 2009·Molecular Cancer Therapeutics·Joan M CarboniMarco M Gottardis
Mar 18, 2010·Endocrine-related Cancer·Karin JennbackenKarin Welén
Apr 21, 2010·Current Opinion in Endocrinology, Diabetes, and Obesity·Jason E Faris, Matthew R Smith
Jun 18, 2010·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Li WangChunyou Wang
Oct 1, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J FlanaganC J Sweeney
Jul 13, 2011·Cancer Research·Amy A LubikColleen C Nelson
Sep 1, 2011·Clinical & Experimental Metastasis·Kyoko Kushiro, Nomelí P Núñez
Dec 14, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Johanna C BendellJosé Baselga
Feb 16, 2012·Prostate Cancer and Prostatic Diseases·R S PriceL A deGraffenried
May 2, 2012·Advances in Urology·Jennifer H GunterColleen C Nelson
Jun 23, 2012·Nature·Catherine S GrassoScott A Tomlins
Aug 17, 2012·The New England Journal of Medicine·Howard I ScherUNKNOWN AFFIRM Investigators
Jan 16, 2013·Endocrine-related Cancer·Amy A LubikColleen C Nelson
Mar 5, 2013·Endocrine-related Cancer·Rhonda L Bitting, Andrew J Armstrong
Apr 11, 2013·Endocrine-related Cancer·Rosalyn D FergusonDerek LeRoith
Apr 11, 2013·International Journal of Cell Biology·Jennifer H GunterColleen C Nelson
Jul 24, 2013·Molecular and Cellular Biology·Konstantin I IvanovTatiana V Petrova
Feb 20, 2014·Frontiers in Endocrinology·Roberta Malaguarnera, Antonino Belfiore
Jul 6, 2014·Advanced Drug Delivery Reviews·Gabriel BentonJennifer Koblinski

❮ Previous
Next ❯

Citations

Jun 7, 2020·International Journal of Molecular Sciences·Milad AshrafizadehGautam Sethi
Sep 11, 2020·Nature Reviews. Cancer·Emily J Gallagher, Derek LeRoith
Feb 20, 2021·Frontiers in Oncology·Tiffany ScullyEmily Jane Gallagher
Mar 26, 2021·Biomicrofluidics·P M GraybillR Mirzaeifar
Apr 17, 2021·Journal of the Association for Research in Otolaryngology : JARO·Tomomi Yamamoto-FukudaHiromi Kojima
May 1, 2021·Cancers·Miłosz KnuraTomasz Francuz
Jul 27, 2021·Current Opinion in Pharmacology·Antonio J León-GonzálezRaúl M Luque

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
Feature Extraction
Protein Assay

Clinical Trials Mentioned

NCT02614859
NCT01796028
NCT01677897

Software Mentioned

Oncomine
LIMMA
Agilent Feature Extraction
GenePattern
GraphPad Prism
GraphPad

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Antidiabetic Cellular Plasticity

This feed focuses on mechanisms that underlie cellular plasticity as a treatment for diabetes and other degenerative diseases.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.