The role of dual oxidases in physiology and cancer

Faria, Caroline Coelho de; Fortunato, Rodrigo S.

doi:10.1590/1678-4685/gmb-2019-0096

Cited by 18 publications

(13 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an NADPH oxidase, Nox1 has been implicated in the regulation of gene expression and ROS generation (11). In addition, a recent study uncovered that upregulation of Nox1 was critical for elevated glycolysis by providing additional NAD+ in cancer cells with mitochondrial dysfunction (12,13). Here, we showed that Nox1 was upregulated in TR CRC cells, which showed apparently elevated glucose metabolism.…”

Section: Discussionmentioning

confidence: 55%

“…NOXs are a family of membrane-associated enzymes which catalyze the oxidation of NADPH or NADH to NADP+ or NAD+ (11). NADPH oxidase 1 (Nox1) belongs to the NOX family and is a multifunctional protein participating in diverse tumor processes, including tumorigenesis, invasion, metastasis, and drug resistance (12). Remarkably, accumulating studies have demonstrated that Nox1 functions as an oncogenic protein with frequent upregulation in diverse tumors (13), indicating that Nox1 could be a therapeutic target for anti-CRC treatments.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Attenuating glucose metabolism by Fbxw7 promotes Taxol sensitivity of colon cancer cells through downregulating NADPH oxidase 1 (Nox1)

Wang¹,

Chen²,

Shen³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

Background: Colorectal cancer (CRC), one of the most common malignancies worldwide, is associated with poor survival and has a high mortality rate. Taxol is a chemotherapeutic agent that has been clinically applied as a first-line drug against diverse cancers. Yet, development of drug resistance has become the major challenge for anti-cancer treatments. F-box and WD40 domain protein 7 (Fbxw7) is a known tumor suppressor which is frequently downregulated in cancers. However, the biological roles and mechanisms of Fbxw7 in Taxol resistance are still under investigation.Methods: We report that Fbxw7 is significantly inactivated in CRC tumors and cell lines compared with normal tissues and colon cells. Expressions of Fbxw7 and Nox1 were detected from human colon tumors and cells by qRT-PCR and Western blot. Glycolysis rate was assessed by glucose uptake and lactate product assay. Interactions between Fbxw7 and Nox1 were determined by co-immunoprecipitation (Co-IP).Chemosensitivity and resistance of colon cancer cells were determined by MTT assay and Annexin V-FITC assay.Results: Overexpression of Fbxw7 sensitized colon cancer cells to Taxol. Moreover, we observed a negative correlation between Fbxw7 and glucose metabolism. From the established Taxol-resistant (TR) cell line from HCT-116, Fbxw7 was found to be markedly downregulated in HCT-116 TR cells. We detected that NADPH oxidase 1 (Nox1), a superoxide-generating NADPH oxidase, is negatively regulated by Fbxw7. The Co-IP assay showed that Fbxw7 interacted with Nox1, which was observed to be significantly upregulated in CRC tissues. Nox1 therefore promotes the Taxol resistance and glucose metabolism of colon cancer cells.Finally, rescue experiments demonstrated that the Fbxw7-promoted Taxol sensitivity was partially through the Nox1-glycolysis axis. Restoration of Nox1 in Fbxw7-overexpressed TR colon cancer cells significantly recovered the Taxol resistance, which could be further overridden by glycolysis inhibition.Conclusions: Collectively, this study uncovered that targeting the Fbxw7-Nox1-glucose metabolism axis could be an effective strategy against chemoresistant colon cancer.

show abstract

Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Attenuating glucose metabolism by Fbxw7 promotes Taxol sensitivity of colon cancer cells through downregulating NADPH oxidase 1 (Nox1)

Wang¹,

Chen²,

Shen³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…Moreover, the generation of ROS is widely known to be an indicator of cancer progression [ 142 ]. Elevated ROS caused by TM4SF1 downregulation can induce cell cycle arrest and apoptosis in human BCa [ 77 ].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance

Rahim

Sim

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

There are six members of the transmembrane 4 superfamily (TM4SF) that have similar topology and sequence homology. Physiologically, they regulate tissue differentiation, signal transduction pathways, cellular activation, proliferation, motility, adhesion, and angiogenesis. Accumulating evidence has demonstrated, among six TM4SF members, the regulatory roles of transmembrane 4 L6 domain family members, particularly TM4SF1, TM4SF4, and TM4SF5, in cancer angiogenesis, progression, and chemoresistance. Hence, targeting derailed TM4SF for cancer therapy has become an emerging research area. As compared to others, this review aimed to present a focused insight and update on the biological roles of TM4SF1, TM4SF4, and TM4SF5 in the progression, metastasis, and chemoresistance of various cancers. Additionally, the mechanistic pathways, diagnostic and prognostic values, and the potential and efficacy of current anti-TM4SF antibody treatment were also deciphered. It also recommended the exploration of other interactive molecules to be implicated in cancer progression and chemoresistance, as well as potential therapeutic agents targeting TM4SF as future perspectives. Generally, these three TM4SF members interact with different integrins and receptors to significantly induce intracellular signaling and regulate the proliferation, migration, and invasion of cancer cells. Intriguingly, gene silencing or anti-TM4SF antibody could reverse their regulatory roles deciphered in different preclinical models. They also have prognostic and diagnostic value as their high expression was detected in clinical tissues and cells of various cancers. Hence, TM4SF1, TM4SF4, and TM4SF5 are promising therapeutic targets for different cancer types preclinically and deserve further investigation.

show abstract

“…In addition, overexpression of extracellular but not intracellular Catalase 10 reduces Idgf3 induction via JNK, indicating that Idgf3 might be regulated via the secretory pathway. Duox and Nox, present in secretory glands, are transmembrane proteins that may generate extracellular ROS (Faria and Fortunato 2020). Their conserved function has been shown to facilitate tumor progression but whether they play an important role in Ras V12 SGs remains to be elucidated (Aggarwal, Tuli et al 2019).…”

Section: Ros Promotes Idgf3 Induction Via Jnkmentioning

confidence: 99%

Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles

Khalili

Kunc

Herbrich

et al. 2022

Preprint

View full text Add to dashboard Cite

Chitinase-like proteins (CLPs) are associated with tissue-remodelling and inflammation but also with several disorders, including fibrosis, atherosclerosis, allergies, and cancer. However, the CLP's role in tumors is far from clear. Here, we utilize Drosophila melanogaster to investigate the function of CLPs (imaginal disc growth factors; Idgf's) in RasV12 dysplastic salivary glands (SGs). We find one of the Idgf's members, Idgf3, to be transcriptionally induced in a tissue- and cell-autonomously manner in a Drosophila hypertrophic model for early tumor progression. Induction involves non-canonical JNK-signaling via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization, independent of Rab5 and Rab11. The process is mediated via Rac1 and the downstream component,Spectrin, which localizes to the EnVs. Similar to Idgf3, expression of two human members of the CLP family in Drosophila SGs aggravates tumor-related phenotypes. Our data provide new insight into a phylogenetically conserved tissue-autonomous CLP function in tumors and identify specific targets for tumor control.

show abstract

The role of dual oxidases in physiology and cancer

Cited by 18 publications

References 89 publications

Attenuating glucose metabolism by Fbxw7 promotes Taxol sensitivity of colon cancer cells through downregulating NADPH oxidase 1 (Nox1)

Attenuating glucose metabolism by Fbxw7 promotes Taxol sensitivity of colon cancer cells through downregulating NADPH oxidase 1 (Nox1)

Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance

Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles

Contact Info

Product

Resources

About