PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity

Gozgit, Joseph M.; Vasbinder, Melissa M.; Abo, Ryan; Kunii, Kaiko; Kuplast-Barr, Kristy; Gui, B.; Lu, Alvin Z.; Molina, Jennifer R.; Minissale, Elena; Swinger, Kerren K.; Wigle, Tim J.; Blackwell, Danielle J.; Majer, Christina R.; Ren, Yue; Niepel, Mario; Varsamis, Zacharenia A.; Nayak, Sunaina P.; Bamberg, Ellen; Mo, Jan-Rung; Church, W. David; Mady, Ahmed S.A.; Song, Jeff; Utley, Luke; Rao, Patricia E.; Mitchison, Timothy J.; Kuntz, Kevin W.; Richon, Victoria M.; Keilhack, Heike

doi:10.1016/j.ccell.2021.06.018

Cited by 92 publications

(160 citation statements)

References 57 publications

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“…In the beginning years, the developed inhibitors were designed targeting a group of ART enzymes; in recent years, novel compounds have been developed specific for a single ART enzyme, with effects at nanomolar concentration. For instance, there are new inhibitors targeting just ARTD10 [120,[127][128][129][130], ARTD11 [122,[131][132][133][134][135][136][137][138][139][140][141][142][143][144]. or ARTD14/PARP7 [142][143][144].…”

Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsmentioning

confidence: 99%

“…For instance, there are new inhibitors targeting just ARTD10 [120,[127][128][129][130], ARTD11 [122,[131][132][133][134][135][136][137][138][139][140][141][142][143][144]. or ARTD14/PARP7 [142][143][144].…”

Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsunclassified

“…ARTD14/PARP7 is amplified and highly expressed in squamous cell carcinomas, in ovarian and lung tumors, and is associated with poor survival [135][136][137]. Protein substrates MARylation, such as α-tubulin, by ARTD14/PARP7, has a role in microtubule control in ovarian cancer [138,143,144]. The enzymes are also involved in maintenance of stemness and pluripotency [139].…”

Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsmentioning

confidence: 99%

“…PARP-7 MARylates immune-relevant protein targets and modulates cancer-directed host immune responses [140]. RBN-2397 specific inhibition of ARTD14 suppresses cell proliferation and activates type-I IFN pathway in cancer cells [141][142][143][144]. RBN-2397 is in a phase 1 clinical trial for patients with advanced solid tumors (Identifier: NCT04053673).…”

Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsmentioning

confidence: 99%

“…lung cancer), and cells with high baseline expression of interferon (IFN)-stimulated genes. Interestingly, RBN-2397 enhanced IFN signaling and induced both cancer cell-autonomous and immune-stimulatory effects [142][143][144].…”

Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsmentioning

confidence: 99%

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Adp-Ribosylation as Post-Translational Modification of Proteins: Use of Inhibitors in Cancer Control

Poltronieri¹,

Misawa²,

Masutani³

2021

Preprint

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Among post-translational modifications of proteins, ADP-ribosylation has been studied for over fifty years, assigning to this PTM a large set of functions, including DNA repair, transcription and cell signaling. This review presents an update on the function of a large set of enzyme writers, the readers that are recruited by the modified targets, and the erasers that reverse the modification to the original amino acid residue, removing the covalent bonds formed. In particular, the review provides details on the involvement of the enzymes performing MAR/PAR cycling in cancers. Of note, there is potential for application of the inhibitors developed for cancer also in the therapy of non-oncological diseases such as the protection against oxidative stress, suppression of inflammatory responses, and the treatment of neurodegenerative diseases. This field of studies is not concluded, since novel enzymes are being discovered at a rapid pace.

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Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsmentioning

confidence: 99%

Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsunclassified

Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsmentioning

confidence: 99%

Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsmentioning

confidence: 99%

Section: Other Marylating Art Enzymes Linked To Cancer and Potential Enzyme Inhibitorsmentioning

confidence: 99%

See 3 more Smart Citations

Adp-Ribosylation as Post-Translational Modification of Proteins: Use of Inhibitors in Cancer Control

Poltronieri¹,

Misawa²,

Masutani³

2021

Preprint

View full text Add to dashboard Cite

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Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype

Enbergs,

Halabi,

Goubet

et al. 2024

Advanced Science

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Tumor‐associated macrophages (TAM) are a diverse population of myeloid cells that are often abundant and immunosuppressive in human cancers. CXCL9Hi TAM has recently been described to have an antitumor phenotype and is linked to immune checkpoint response. Despite the emerging understanding of the unique antitumor TAM phenotype, there is a lack of TAM‐specific therapeutics to exploit this new biological understanding. Here, the discovery and characterization of multiple small‐molecule enhancers of chemokine ligand 9 (CXCL9) and their targeted delivery in a TAM‐avid systemic nanoformulation is reported. With this strategy, it is efficient encapsulation and release of multiple drug loads that can efficiently induce CXCL9 expression in macrophages, both in vitro and in vivo in a mouse tumor model. These observations provide a window into the molecular features that define TAM‐specific states, an insight a novel therapeutic anticancer approach is used to discover.

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Revisiting the role of endogenous STAT3 in HPV‐positive cervical cancer cells

Strobel,

Weber,

Heber

et al. 2023

Journal of Medical Virology

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Novel treatment options for human papillomavirus (HPV)‐induced cancers are urgently required. The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is considered to be constitutively active in HPV‐positive cervical cancer cells and essential for their proliferation. Moreover, STAT3 was reported to undergo mutually stimulatory interactions with the HPV E6/E7 oncogenes. Thus, inhibiting STAT3 in HPV‐positive cancer cells is under discussion to provide a powerful novel therapeutic strategy. We here show that the antifungal drug ciclopirox destabilizes the STAT3 protein by acting as an iron chelator. However, by exploring the functional consequences of STAT3 inhibition in HPV‐positive cancer cells, we obtained several unexpected results. Chemical STAT3 inhibitors heterogeneously affect cervical cancer cell proliferation and those which act antiproliferative also block the growth of STAT3 knockout cells, indicating induction of off‐target effects. In contrast to several chemical inhibitors, genetic inhibition of STAT3 expression by either RNA interference or the CRISPR/Cas9 method does not appreciably affect cervical cancer cell proliferation. Transcriptome analyses indicate that blocking STAT3 expression in HPV‐positive cancer cells has very limited effects on putative STAT3 target genes. Although the targeted inhibition of specific growth‐promoting signaling pathways leads to a feedback activation of STAT3 in cervical cancer cells via Janus kinase 1/2, this does not lead to treatment resistance. Moreover, we did not obtain experimental evidence for a STAT3‐linked activation of HPV E6/E7 oncogene expression or, vice versa, an E6/E7‐dependent activation of STAT3, at endogenous conditions in cervical cancer cells. Collectively, these findings question the essential role of STAT3 in cervical cancer cell proliferation and the strategy to inhibit STAT3 in these cells for therapeutic purposes.

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PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity

Cited by 92 publications

References 57 publications

Adp-Ribosylation as Post-Translational Modification of Proteins: Use of Inhibitors in Cancer Control

Adp-Ribosylation as Post-Translational Modification of Proteins: Use of Inhibitors in Cancer Control

Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype

Revisiting the role of endogenous STAT3 in HPV‐positive cervical cancer cells

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