Toll-like receptor 2 orchestrates a tumor suppressor response in non-small cell lung cancer

Millar, Fraser R.; Pennycuick, Adam; Muir, Morwenna; Quintanilla, Andrea; Hari, Priya; Freyer, Elisabeth; Gautier, Philippe; Meynert, Alison; Grimes, Graeme R.; Coll, Carla Salomo; Zdral, Sofía; Victorelli, Stella; Teixeira, Vítor Hugo; Connelly, John C.; Passos, João F.; Ros, María A.; Wallace, William; Frame, Margaret C.; Sims, Andrew H.; Boulter, Luke; Janes, Sam M.; Wilkinson, Simon; Acosta, Juan Carlos

doi:10.1016/j.celrep.2022.111596

Cited by 14 publications

(10 citation statements)

References 55 publications

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“…Previous reports suggest that TLR2 agonists can effectively inhibit non-small cell lung cancer . Herein, we identified WYJ-2 as a potent TLR2/1 agonist that can induce pyroptosis of A549 cells in vitro.…”

Section: Resultsmentioning

confidence: 81%

“…Previous reports suggest that TLR2 agonists can effectively inhibit non-small cell lung cancer. 34 Herein, we identified WYJ-2 as a potent TLR2/1 agonist that can induce pyroptosis of A549 cells in vitro. Therefore, we established a subcutaneous A549 tumor-bearing mice model to evaluate the anti-lung cancer activity of WYJ-2 in vivo.…”

Section: Evaluation Of Downstream Cytokinesmentioning

confidence: 94%

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Design and Synthesis of 3-(2H-Chromen-3-yl)-5-aryl-1,2,4-oxadiazole Derivatives as Novel Toll-like Receptor 2/1 Agonists That Inhibit Lung Cancer In Vitro and In Vivo

Wang,

Cheng,

Liu

et al. 2024

J. Med. Chem.

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Toll-like receptor (TLR) 2 is a transmembrane receptor that participates in the innate immune response by forming a heterodimer with TLR1 or TLR6. TLR2 agonists play an important role in tumor therapy. Herein, we synthesized a series of 3-(2Hchromen-3-yl)-5-aryl-1,2,4-oxadiazole derivatives and identified WYJ-2 as a potent small and selective molecule agonist of TLR2/1, with an EC 50 of 18.57 ± 0.98 nM in human TLR2 and TLR1 transient-cotransfected HEK 293T cells. WYJ-2 promoted the formation of TLR2/1 heterodimers and activated the nuclear factor kappa B (NF-κB) signaling pathway. Moreover, our study indicated that WYJ-2 could induce pyroptosis in cancer cells, mediated by activating the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. WYJ-2 exhibited effective anti-non-small cell lung cancer (NSCLC) activity in vitro and in vivo. The discovery that activating TLR2/1 induces pyroptosis in cancer cells may highlight the prospects of TLR2/1 agonists in cancer treatment in the future.

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Section: Resultsmentioning

confidence: 81%

Section: Evaluation Of Downstream Cytokinesmentioning

confidence: 94%

Design and Synthesis of 3-(2H-Chromen-3-yl)-5-aryl-1,2,4-oxadiazole Derivatives as Novel Toll-like Receptor 2/1 Agonists That Inhibit Lung Cancer In Vitro and In Vivo

Wang,

Cheng,

Liu

et al. 2024

J. Med. Chem.

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“…Cellular senescence is a state of permanent growth arrest and is thought to be an essential anticarcinogenic barrier in normal cells. Cellular senescence protects tissues from developing cancer by arresting the cell cycle [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Senescence can also create an inflammatory microenvironment favoring the initiation and progression of various age-related diseases including cancer [ 9 ].…”

Section: Characteristics Of Senescencementioning

confidence: 99%

“…OIS increased cytoplasmic release of cytochrome c, the expression of BAX, and the cleavage of poly(ADP-ribose) polymerase (PARP) in human keratinocytes [ 50 ]. During OIS, Toll-like receptor 2 (TLR2) was shown to mediate senescence in vitro and in murine models [ 3 ]. TLR2 impairs early lung cancer progression by activating cell cycle arrest and the pro-inflammatory phenotype [ 3 ].…”

Section: Oncogene-induced Senescencementioning

confidence: 99%

“…During OIS, Toll-like receptor 2 (TLR2) was shown to mediate senescence in vitro and in murine models [ 3 ]. TLR2 impairs early lung cancer progression by activating cell cycle arrest and the pro-inflammatory phenotype [ 3 ]. TLR2 promoted cell cycle arrest by increasing the expression of tumor suppressors (p53-p21CIP1, p16INK4a, and p15INK4b) by inducing the acute-phase serum amyloids A1 and A2 (A-SAAs) [ 51 ].…”

Section: Oncogene-induced Senescencementioning

confidence: 99%

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The Potential of Senescence as a Target for Developing Anticancer Therapy

Shim

Jeoung

2023

IJMS

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Senescence occurs in response to various stimuli. Senescence has attracted attention because of its potential use in anticancer therapy as it plays a tumor-suppressive role. It also promotes tumorigeneses and therapeutic resistance. Since senescence can induce therapeutic resistance, targeting senescence may help to overcome therapeutic resistance. This review provides the mechanisms of senescence induction and the roles of the senescence-associated secretory phenotype (SASP) in various life processes, including therapeutic resistance and tumorigenesis. The SASP exerts pro-tumorigenic or antitumorigenic effects in a context-dependent manner. This review also discusses the roles of autophagy, histone deacetylases (HDACs), and microRNAs in senescence. Many reports have suggested that targeting HDACs or miRNAs could induce senescence, which, in turn, could enhance the effects of current anticancer drugs. This review presents the view that senescence induction is a powerful method of inhibiting cancer cell proliferation.

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Implication of Toll-Like Receptors in growth and management of health and diseases: Special focus as a promising druggable target to Prostate Cancer

Khan,

Simsek,

Fuentes

et al. 2025

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Toll-like receptor 2 orchestrates a tumor suppressor response in non-small cell lung cancer

Cited by 14 publications

References 55 publications

Design and Synthesis of 3-(2H-Chromen-3-yl)-5-aryl-1,2,4-oxadiazole Derivatives as Novel Toll-like Receptor 2/1 Agonists That Inhibit Lung Cancer In Vitro and In Vivo

Design and Synthesis of 3-(2H-Chromen-3-yl)-5-aryl-1,2,4-oxadiazole Derivatives as Novel Toll-like Receptor 2/1 Agonists That Inhibit Lung Cancer In Vitro and In Vivo

The Potential of Senescence as a Target for Developing Anticancer Therapy

Implication of Toll-Like Receptors in growth and management of health and diseases: Special focus as a promising druggable target to Prostate Cancer

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