ArticleOncotarget2014
NEK2 mediates ALDH1A1-dependent drug resistance in multiple myeloma.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- Reduced ALDH1A1 expression in multiple myeloma cells increases resistance to daratumumab via downregulation of retinoic acid.Cellular and molecular life sciences : CMLS · 2025Article
- ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review).Oncology letters · 2025Review
- NEK2 promotes the progression of osteosarcoma through the AKT/p-AKT pathway and interacts with FoxM1.Medical oncology (Northwood, London, England) · 2025Article
- Prognostic implications of MUC1 and XBP1 concordant expression in multiple myeloma: A retrospective study.PloS one · 2025Article
- Autophagy unrelated transcriptional mechanisms of hydroxychloroquine resistance revealed by integrated multi-omics of evolved cancer cells.Cell cycle (Georgetown, Tex.) · 2024Article
- Stem Cell Origin of Cancer: Clinical Implications beyond Immunotherapy for Drug versus Therapy Development in Cancer Care.Cancers · 2024Article
- The Aryl Hydrocarbon Receptor: Impact on the Tumor Immune Microenvironment and Modulation as a Potential Therapy.Cancers · 2024Review
- Identification of a novel spirocyclic Nek2 inhibitor using high throughput virtual screening.Bioorganic & medicinal chemistry letters · 2023Article
- Past, Present, and a Glance into the Future of Multiple Myeloma Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Response to primary chemoradiotherapy of locally advanced oropharyngeal carcinoma is determined by the degree of cytotoxic T cell infiltration within tumor cell aggregates.Frontiers in immunology · 2023Article
- In Mitosis You Are Not: The NIMA Family of Kinases inInternational journal of molecular sciences · 2022Review
- Effect ofInternational journal of molecular sciences · 2022Article
- Genetic Aberrations and Interaction of NEK2 and TP53 Accelerate Aggressiveness of Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Nek2 Kinase Signaling in Malaria, Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development.Molecules (Basel, Switzerland) · 2022Review
- Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies.Antioxidants (Basel, Switzerland) · 2021Review
- Review
- CHEK1 and circCHEK1_246aa evoke chromosomal instability and induce bone lesion formation in multiple myeloma.Molecular cancer · 2021Article
- Review
- High expression of NEK2 promotes gastric cancer progression via activating AKT signaling.Journal of physiology and biochemistry · 2021Article
- Markers and Reporters to Reveal the Hierarchy in Heterogeneous Cancer Stem Cells.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
We reported previously that increased expression of aldehyde dehydrogenase 1 (ALDH1) in multiple myeloma (MM) is a marker of tumor-initiating cells (TICs) that is further associated with chromosomal instability (CIN). Here we demonstrate that member A1 of the ALDH1 family of proteins, ALDH1A1, is most abundantly expressed in myeloma. Enforced expression of ALDH1A1 in myeloma cells led to increased clonogenicity, tumor formation in mice, and resistance to myeloma drugs in vitro and in vivo. The mechanism underlying these phenotypes included the ALDH1A1-dependent activation of drug-efflux pump, ABCB1, and survival proteins, AKT and BCL2. Over expression of ALDH1A1 in myeloma cells led to increased mRNA and protein levels of NIMA-related kinase 2 (NEK2), whereas shRNA-mediated knock down of NEK2 decreased drug efflux pump activity and drug resistance. The activation of NEK2 in myeloma cells relied on the ALDH1A1-dependent generation of the retinoid X receptor α (RXRα) ligand, 9-cis retinoic acid (9CRA) - not the retinoic acid receptor α (RARα) ligand, all-trans retinoic acid (ATRA). These findings implicate the ALDH1A1-RXRα-NEK2 pathway in drug resistance and disease relapse in myeloma and suggest that specific inhibitors of ALDH1A1 are worthy of consideration for clinical development of new approaches to overcome drug resistance in myeloma.
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