ArticleJournal of cellular and molecular medicine2022
VLX1570 regulates the proliferation and apoptosis of human lung cancer cells through modulating ER stress and the AKT pathway.
Article in Journal of cellular and molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Ubiquitination and deubiquitination as critical modulators of NSCLC tumorigenesis and drug resistance.Discover oncology · 2026Review
- The role of ubiquitination in the pathogenesis of atrial fibrillation: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- VLX1570 suppresses neuroblastoma growth through inhibition of PCNA-associated proliferative signaling and potentiates cisplatin antitumor activity.Frontiers in pharmacology · 2026Article
- MiR-204-5p mediates PERK inhibition to suppress growth and induce apoptosis in ovarian cancer through the eIF2α/ATF-4/CHOP pathway.Scientific reports · 2025Article
- Afzelin induces immunogenic cell death against lung cancer by targeting NQO2.BMC complementary medicine and therapies · 2023Article
- Inhibition of CDK1 by RO-3306 Exhibits Anti-Tumorigenic Effects in Ovarian Cancer Cells and a Transgenic Mouse Model of Ovarian Cancer.International journal of molecular sciences · 2023Article
- Ubiquitin-proteasome system as a target for anticancer treatment-an update.Archives of pharmacal research · 2023Review
- The Ubiquitin-Proteasome System in Tumor Metabolism.Cancers · 2023Review
- The roles of protein ubiquitination in tumorigenesis and targeted drug discovery in lung cancer.Frontiers in endocrinology · 2023Review
- VLX1570 regulates the proliferation and apoptosis of human lung cancer cells through modulating ER stress and the AKT pathway.Journal of cellular and molecular medicine · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
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Abstract
The ubiquitin-proteasome system (UPS) possesses unique functions in tumorigenesis and has great potential for targeting tumours. The effectiveness of inhibitors targeting UPS in solid tumours remains to be studied. We screened a library of inhibitors targeting the ubiquitination system and found the highly potent, low-concentration inhibitor molecule VLX1570 that specifically killed lung cancer cells. VLX1570 is an inhibitor of deubiquitinating enzyme activity and has also shown potential for preclinical cancer treatment. We found that VLX1570 significantly inhibited lung cancer cells proliferation and colony formation. VLX1570 induced a G2/M cell cycle arrest by downregulating CDK1 and CyclinB1. Moreover, VLX1570 significantly promoted the mitochondrial-associated apoptosis. Mechanistically speaking, VLX1570 activated the PERK/IRE1/ATF6 pathway and induced ER stress in lung cancer cell lines. The inhibition of ER stress by tauroursodeoxycholic acid sodium or 4-phenylbutyric acid enhanced VLX1570-induced apoptosis. In addition, VLX1570 treatment led to the inactivation of Akt signalling and inhibited the proliferation of lung cancer cells by downregulating the Akt pathway. Moreover, combined treatment with VLX1570 and Afatinib or Gefitinib induced synergistic anti-lung cancer activity. Our present study demonstrated a novel therapy using VLX1570, which inhibited the proliferation and increased apoptosis in human lung cancer.
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