COMMD1, from the Repair of DNA Double Strand Breaks, to a Novel Anti-Cancer Therapeutic Target

Suraweera, Amila; Duijf, Pascal H.G.; Jekimovs, Christian; Schrobback, Karsten; Cheng, Liang; Adams, Mark N.; O’Byrne, Kenneth J.; Richard, Derek J.

doi:10.3390/cancers13040830

Cited by 5 publications

(4 citation statements)

References 66 publications

(106 reference statements)

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“…COMMD1 is the most extensively characterised COMMD protein and is a pleiotropic factor, regulating many biological processes, including copper and cholesterol homoeostasis, ionic transport, protein aggregation, protein trafficking, oncogenesis, and oxidative stress 14 . Futhermore, COMMD1 was recently shown to function in the repair of DSBs and be a potential therapeutic target for the treatment of non-small cell lung cancer 15 . COMMD4, the subject of this study, has been previously shown to control NFkB activity in mammals 16 , to interact with cullins and modulate the activity of cullin-RING E3 ubiquitin ligase complexes 17 and be a good prognostic marker and therapeutic target in non-small cell lung cancer 18 .…”

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confidence: 99%

COMMD4 Functions with the Histone H2A-H2B Dimer for the Timely Repair of DNA Double Strand Breaks

et al. 2020

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Genomic stability is critical for normal cellular function and its deregulation is a universal hallmark of cancer. Here we outline a previously undescribed role of COMMD4 in maintaining genomic stability, by regulation of chromatin remodelling at sites of DNA double-strand breaks. At break-sites, COMMD4 binds to and protects histone H2B from monoubiquitination by RNF20/RNF40. DNA damage-induced phosphorylation of the H2A-H2B heterodimer disrupts the dimer allowing COMMD4 to preferentially bind H2A. Displacement of COMMD4 from H2B allows RNF20/40 to monoubiquitinate H2B and for remodelling of the break-site. Consistent with this critical function, COMMD4-deficient cells show excessive elongation of remodelled chromatin and failure of both non-homologousend-joining and homologous recombination. We present peptide-mapping and mutagenesis data for the potential molecular mechanisms governing COMMD4-mediated chromatin regulation at DNA double-strand breaks.

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COMMD4 Functions with the Histone H2A-H2B Dimer for the Timely Repair of DNA Double Strand Breaks

et al. 2020

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“…The research also revealed that the upregulation of COMMD1 increased the proliferation of NSCLC cells and was associated with a bad prognosis for patients. Even COMMD1 -knockdown might increase the radiation sensitivity of NSCLC cells ( 17 ). As a potential novel anticancer treatment target, the function of COMMD1 in NSCLC requires additional investigation.…”

Section: The Commd Protein Family and Tumorsmentioning

confidence: 99%

“…Although the majority of molecular mechanism research have focused on COMMD1, nearly all COMMD protein family members regulate tumor progression. For example, COMMD1 ( 17 ), COMMD4 ( 18 ), COMMD8 ( 19 ), and COMMD9 ( 20 ) regulate the proliferation, invasion, and metastasis of lung cancer. COMMD2 ( 21 ), COMMD3 ( 22 ), COMMD7 ( 23 ), COMMD8 ( 24 ), and COMMD10 ( 25 ) promote or inhibit hepatocellular carcinoma (HCC).…”

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confidence: 99%

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COMMD proteins function and their regulating roles in tumors

et al. 2023

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The COMMD proteins are a highly conserved protein family with ten members that play a crucial role in a variety of biological activities, including copper metabolism, endosomal sorting, ion transport, and other processes. Recent research have demonstrated that the COMMD proteins are closely associated with a wide range of disorders, such as hepatitis, myocardial ischemia, cerebral ischemia, HIV infection, and cancer. Among these, the role of COMMD proteins in tumors has been thoroughly explored; they promote or inhibit cancers such as lung cancer, liver cancer, gastric cancer, and prostate cancer. COMMD proteins can influence tumor proliferation, invasion, metastasis, and tumor angiogenesis, which are strongly related to the prognosis of tumors and are possible therapeutic targets for treating tumors. In terms of molecular mechanism, COMMD proteins in tumor cells regulate the oncogenes of NF-κB, HIF, c-MYC, and others, and are related to signaling pathways including apoptosis, autophagy, and ferroptosis. For the clinical diagnosis and therapy of malignancies, additional research into the involvement of COMMD proteins in cancer is beneficial.

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COMMD10 inhibited DNA damage to promote the progression of gastric cancer

Liu,

Mao,

Zhu

et al. 2024

J Cancer Res Clin Oncol

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Purpose The copper metabolism MURR1 domain 10 (COMMD10) plays a role in a variety of tumors. Here, we investigated its role in gastric cancer (GC). Methods Online prediction tools, quantitative real-time PCR, western blotting and immunohistochemistry were used to evaluate the expression of COMMD10 in GC. The effect of COMMD10 knockdown was investigated in the GC cell lines and in in vivo xenograft tumor experiments. Western blotting and immunofluorescence were used to explore the relationships between COMMD10 and DNA damage. Results The expression of COMMD10 was upregulated in GC compared to that in para-cancerous tissue and correlated with a higher clinical TNM stage (P = 0.044) and tumor size (P = 0.0366). High COMMD10 expression predicted poor prognosis in GC. Knockdown of COMMD10 resulted in the suppression of cell proliferation, migration, and invasion, accompanied by cell cycle arrest and an elevation in apoptosis rate. Moreover, the protein expression of COMMD10 was decreased in cisplatin-induced DNA-damaged GC cells. Suppression of COMMD10 impeded DNA damage repair, intensified DNA damage, and activated ATM–p53 signaling pathway in GC. Conversely, restoration of COMMD10 levels suppressed DNA damage and activation of the ATM-p53 signaling cascade. Additionally, knockdown of COMMD10 significantly restrained the growth of GC xenograft tumors while inhibiting DNA repair, augmenting DNA damage, and activating the ATM–p53 signaling pathway in xenograft tumor tissue. Conclusion COMMD10 is involved in DNA damage repair and maintains genomic stability in GC; knockdown of COMMD10 impedes the development of GC by exacerbating DNA damage, suggesting that COMMD10 may be new target for GC therapy.

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COMMD1, from the Repair of DNA Double Strand Breaks, to a Novel Anti-Cancer Therapeutic Target

Cited by 5 publications

References 66 publications

COMMD4 Functions with the Histone H2A-H2B Dimer for the Timely Repair of DNA Double Strand Breaks

COMMD4 Functions with the Histone H2A-H2B Dimer for the Timely Repair of DNA Double Strand Breaks

COMMD proteins function and their regulating roles in tumors

COMMD10 inhibited DNA damage to promote the progression of gastric cancer

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