ArticleProceedings of the National Academy of Sciences of the United States of America2020
Multiple myeloma cells are exceptionally sensitive to heat shock, which overwhelms their proteostasis network and induces apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Exploiting tumor lineage features for precision cancer therapy.Trends in cancer · 2026Review
- Chloroplast: structural and functional alteration under nickel stress and tolerance mechanism via the omics approach.Plant cell reports · 2026Review
- Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Structural insights into the ubiquitin-independent midnolin-proteasome pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Viable mutations of mouse midnolin suppress B cell malignancies.The Journal of experimental medicine · 2024Article
- Acute suppression of translation by hyperthermia enhances anti-myeloma activity of carfilzomib.International journal of hematology · 2024Article
- Photothermal Fibrous Chitosan/Polydopamine Sponge for Intraoperative Hemostasis and Prevention of Tumor Recurrence in Hepatocellular Carcinoma Resection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Factors determining the sensitivity to proteasome inhibitors of multiple myeloma cells.Frontiers in pharmacology · 2024Review
- Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis.Blood · 2023Article
- 26S proteasomes become stably activated upon heat shock when ubiquitination and protein degradation increase.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Selective vulnerabilities in the proteostasis network of castration-resistant prostate cancer.Cell chemical biology · 2022Article
- A drug repurposing strategy for overcoming human multiple myeloma resistance to standard-of-care treatment.Cell death & disease · 2022Article
- Review
- Advances in Proteasome Enhancement by Small Molecules.Biomolecules · 2021Review
- Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review).International journal of oncology · 2021Review
- Quantitative Ultrasound for Evaluation of Tumour Response to Ultrasound-Microbubbles and Hyperthermia.Technology in cancer research & treatmentArticle
- Emerging roles of DYRK2 in cancer.The Journal of biological chemistryReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Proteasome inhibitors, such as bortezomib (BTZ), are highly effective and widely used treatments for multiple myeloma. One proposed reason for myeloma cells' exceptional sensitivity to proteasome inhibition is that they produce and continually degrade unusually large amounts of abnormal immunoglobulins. We, therefore, hypothesized that, heat shock may also be especially toxic to myeloma cells by causing protein unfolding, increasing further the substrate load on proteasomes, and, thus, putting further stress on their capacity for protein homeostasis. After a shift from 37 to 43 °C, all four myeloma lines studied underwent extensive apoptosis in 4 h, unlike 13 nonmyeloma cell lines, even though the myeloma cells induced heat-shock proteins and increased protein degradation similar to other cells. Furthermore, two myeloma lines resistant to proteasome inhibitors were also more resistant to 43 °C. Shifting myeloma cells to 43, 41, or 39 °C (which was not cytotoxic) dramatically increased their killing by proteasome inhibitors and inhibitors of ubiquitination or p97/VCP. Combining increased temperature with BTZ increased the accumulation of misfolded proteins and substrate load on the 26S proteasome. The apoptosis seen at 43 °C and at 39 °C with BTZ was mediated by caspase-9 and was linked to an accumulation of the proapoptotic Bcl-2-family member Noxa. Thus, myeloma cells are exceptionally sensitive to increased temperatures, which greatly increase substrate load on the ubiquitin-proteasome system and eventually activate the intrinsic apoptotic pathway. Consequently, for myeloma, mild hyperthermia may be a beneficial approach to enhance the therapeutic efficacy of proteasome inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
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.