ArticleMolecular cancer therapeutics2011
Acquisition of resistance toward HYD1 correlates with a reduction in cleaved α4 integrin expression and a compromised CAM-DR phenotype.
Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Phosphoproteomic Profiling of Multiple Myeloma Based on Ex Vivo Drug Sensitivity Resistance Testing Identifies Phosphorylation Signatures Associated with Drug Response.Biomolecules · 2026Article
- Article
- Bioactivity improvement via display of the hydrophobic core of HYD1 in a cyclic β-hairpin-like scaffold, MTI-101.Peptide science (Hoboken, N.J.) · 2021Article
- Elucidating the expression and function of Numbl during cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma (MM).BMC cancer · 2019Article
- Beta1 integrin blockade overcomes doxorubicin resistance in human T-cell acute lymphoblastic leukemia.Cell death & disease · 2019Article
- MTI-101 treatment inducing activation of Stim1 and TRPC1 expression is a determinant of response in multiple myeloma.Scientific reports · 2017Article
- Targeting Intrinsic and Extrinsic Vulnerabilities for the Treatment of Multiple Myeloma.Journal of cellular biochemistry · 2017Review
- Expression of vaccinia-related kinase 1 (VRK1) accelerates cell proliferation but overcomes cell adhesion mediated drug resistance (CAM-DR) in multiple myeloma.Hematology (Amsterdam, Netherlands) · 2016Article
- Integrin β1-mediated acquired gefitinib resistance in non-small cell lung cancer cells occurs via the phosphoinositide 3-kinase-dependent pathway.Oncology letters · 2016Article
- Review
- Cell adhesion down-regulates the expression of vacuolar protein sorting 4B (VPS4B) and contributes to drug resistance in multiple myeloma cells.International journal of hematology · 2015Article
- Translational horizons in the tumor microenvironment: harnessing breakthroughs and targeting cures.Medicinal research reviews · 2015Review
- A role for activator of G-protein signaling 3 (AGS3) in multiple myeloma.International journal of hematology · 2014Article
- MTI-101 (cyclized HYD1) binds a CD44 containing complex and induces necrotic cell death in multiple myeloma.Molecular cancer therapeutics · 2013Article
- The role of tumour-stromal interactions in modifying drug response: challenges and opportunities.Nature reviews. Drug discovery · 2013Review
- Association of integrin beta1 and c-MET in mediating EGFR TKI gefitinib resistance in non-small cell lung cancer.Cancer cell international · 2013Article
- CRM1 Inhibition Sensitizes Drug Resistant Human Myeloma Cells to Topoisomerase II and Proteasome Inhibitors both In Vitro and Ex Vivo.Journal of Cancer · 2013Article
- Integrin signaling in cancer cell survival and chemoresistance.Chemotherapy research and practice · 2012Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
We recently reported that the β1 integrin antagonist, referred to as HYD1, induces necrotic cell death in myeloma cell lines as a single agent using in vitro and in vivo models. In this article, we sought to delineate the determinants of sensitivity and resistance toward HYD1-induced cell death. To this end, we developed an HYD1 isogenic resistant myeloma cell line by chronically exposing H929 myeloma cells to increasing concentrations of HYD1. Our data indicate that the acquisition of resistance toward HYD1 correlates with reduced levels of the cleaved α4 integrin subunit. Consistent with reduced VLA-4 (α4β1) expression, the resistant variant showed ablated functional binding to fibronectin, VCAM-1, and the bone marrow stroma cell line HS-5. The reduction in binding of the resistant cell line to HS-5 cells translated to a compromised cell adhesion-mediated drug resistant phenotype as shown by increased sensitivity to melphalan- and bortezomib-induced cell death in the bone marrow stroma coculture model of drug resistance. Importantly, we show that HYD1 is more potent in relapsed myeloma specimens than newly diagnosed patients, a finding that correlated with α4 integrin expression. Collectively, these data indicate that this novel d-amino acid peptide may represent a good candidate for pursuing clinical trials in relapsed myeloma and in particular patients with high levels of α4 integrin. Moreover, our data provide further rationale for continued preclinical development of HYD1 and analogues of HYD1 for the treatment of multiple myeloma and potentially other tumors that home and/or metastasize to the bone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.