ArticleOncoscience2014
Integrin αV modulates the cellular pharmacology of copper and cisplatin by regulating expression of the influx transporter CTR1.
Article in Oncoscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Exploring Copper's role in stroke: progress and treatment approaches.Frontiers in pharmacology · 2024Review
- Copper transporters and chaperones: Their function on angiogenesis and cellular signalling.Journal of biosciences · 2016Review
- Transcriptome analysis of copper homeostasis genes reveals coordinated upregulation of SLC31A1,SCO1, and COX11 in colorectal cancer.FEBS open bio · 2016Article
- Integrin αV control of Cu homeostasis and cisplatin sensitivity.Cell cycle (Georgetown, Tex.) · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The αV integrin is expressed in most cancer cells where it regulates a diverse array of cellular functions essential to the initiation, progression and metastasis of solid tumors. However, little is known about how αV integrin modulates cellular sensitivity to chemotherapeutic agents, particularly the platinum drugs. In this study, we found that down-regulation of αV sensitized human M21 cells to cisplatin (cDDP) through up-regulation of the copper influx transporter CTR1. Cells selected for low αV integrin expression (M21L) were more sensitive to cDDP, accompanied by increase in CTR1 mRNA and CTR1 protein levels, more intracellular cDDP accumulation and cDDP DNA adduct formation. Basal copper (Cu) content, Cu uptake, and Cu cytotoxicity were also increased. Transfection of a luciferase reporter construct containing the hCTR1 promoter sequence revealed an increase of the hCTR1 transcription activity in M21L cells. The basis for the increased hCTR1 transcription was related to an increase in the steady-state level of Sp1, a transcription factor known to drive hCTR1 expression. These results indicate that the αV integrin modulates sensitivity of human cells to the cytotoxic effect of cDDP by regulating expression of the Cu transporter CTR1, and introduce the concept that αV expression is linked to Cu homeostasis.
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Registered trials
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