ArticleBritish journal of cancer2012
Resistance to the mTOR-inhibitor RAD001 elevates integrin α2- and β1-triggered motility, migration and invasion of prostate cancer cells.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
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- Starvation-inactivated MTOR triggers cell migration via a ULK1-SH3PXD2A/TKS5-MMP14 pathway in ovarian carcinoma.Autophagy · 2023Article
- Targeting integrin α5β1 in urological tumors: opportunities and challenges.Frontiers in oncology · 2023Review
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- Inhibition by Thyroid Hormones of Cell Migration Activated by IGF-1 and MCP-1 in THP-1 Monocytes: Focus on Signal Transduction Events Proximal to Integrin αvβ3.Frontiers in cell and developmental biology · 2021Article
- Entosis and apical cell extrusion constitute a tumor-suppressive mechanism downstream of Matriptase.The Journal of cell biology · 2020Article
- eEF2 kinase mediated autophagy as a potential therapeutic target for paclitaxel-resistant triple-negative breast cancer.Annals of translational medicine · 2019Article
- Five tumor-associated autoantibodies expression levels in serum predict lung cancer and associate with poor outcome.Translational cancer research · 2019Article
- Overexpression of microRNA-620 facilitates the resistance of triple negative breast cancer cells to gemcitabine treatment by targeting DCTD.Experimental and therapeutic medicine · 2019Article
- Mechanisms behind Temsirolimus Resistance Causing Reactivated Growth and Invasive Behavior of Bladder Cancer Cells In Vitro.Cancers · 2019Article
- Hypoxia-induced PIM kinase and laminin-activated integrin α6 mediate resistance to PI3K inhibitors in bone-metastatic CRPC.American journal of clinical and experimental urology · 2019Article
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- Acquired resistance to temsirolimus is associated with integrin α7 driven chemotactic activity of renal cell carcinomaOncotarget · 2018Article
- C-reactive protein binds to integrin α2 and Fcγ receptor I, leading to breast cell adhesion and breast cancer progression.Oncogene · 2018Article
- Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer.International journal of molecular sciences · 2017Review
- Sulforaphane inhibits proliferation and invasive activity of everolimus-resistant kidney cancer cells in vitro.Oncotarget · 2016Article
- Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy.Cancer science · 2016Article
- Dual PI3K/mTOR inhibitor, XL765 (SAR245409), shows superior effects to sole PI3K [XL147 (SAR245408)] or mTOR [rapamycin] inhibition in prostate cancer cell models.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Article
- CCL2 promotes integrin-mediated adhesion of prostate cancer cells in vitro.World journal of urology · 2015Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInhibitors of the mammalian target of rapamycin (mTOR) might become a novel tool to treat advanced prostate cancer. However, chronic drug exposure may trigger resistance, limiting the utility of mTOR inhibitors.
methodsMetastatic potential of PC3 prostate cancer cells, susceptible (PC3(par)) or resistant (PC3(res)) to the mTOR-inhibitor RAD001 was investigated. Adhesion to vascular endothelium or immobilised collagen, fibronectin and laminin was quantified. Motility, migration and invasion were explored by modified Boyden chamber assay. Integrin α and β subtypes were analysed by flow cytometry, western blotting and real-time PCR. Integrin-related signalling, EGFr, Akt, p70S6kinase and ERK1/2 activation were determined.
resultsAdhesion was reduced, whereas motility, migration and invasion were enhanced in PC3(res). The α2 and β1 integrin subtypes were dramatically elevated, integrins α1 and α6 were lowered, whereas α5 was nearly lost in PC3(res). Activation of the Akt signalling pathway was strongly upregulated in these cells. Treating PC3(par) cells with RAD001 reduced motility, migration and invasion and deactivated Akt signalling. Blocking studies revealed that α2 and β1 integrins significantly trigger the motile behaviour of the tumour cells.
conclusionChronic RAD001 treatment caused resistance development characterised by distinct modification of the integrin-expression profile, driving prostate cancer cells towards high motility.
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