Identification of a Wells–Dawson polyoxometalate-based AP-2γ inhibitor with pro-apoptotic activity

Hu, Jiamiao; Tan, Si Kee; Lim, Michelle Gek Liang; Chang, Shie Hong; Cui, Guimei; Liu, Shanshan; Narasimhan, Kamesh; New, Siu Yee; Wang, Xuecong; Chen, Congling; Chakravarty, Harapriya; Kolatkar, Prasanna R.; Tam, Kin Yip; Lü, Qian; Jauch, Ralf; Cheung, Edwin

doi:10.1042/bcj20170942

Cited by 9 publications

(6 citation statements)

References 52 publications

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“…These findings confirm that AP-2α activity is influenced by tumor tissue type: while it was found to demonstrate oncogenic activity in cervical, gallbladder and ovarian cancer [27][28][29], it has been also seen to act as a suppressor in many other tumors [11,[30][31][32][33][34][35]. AP-2γ has been conclusively demonstrated to play an oncogenic role in breast cancer [36] (which coincides with previous evaluation) and furthermore expanded with its unfavorable characteristics in colorectal cancer [25]. The last representative of the AP-2 family abundantly described in the literature is beta member.…”

Section: Introductionsupporting

confidence: 64%

Functional genomics of AP-2α and AP-2γ in cancers: in silico study

et al. 2020

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Background Among all causes of death, cancer is the most prevalent and is only outpaced by cardiovascular diseases. Molecular theory of carcinogenesis states that apoptosis and proliferation are regulated by groups of tumor suppressors or oncogenes. Transcription factors are example of proteins comprising representatives of both cancer-related groups. Exemplary family of transcription factors which exhibits dualism of function is Activating enhancer-binding Protein 2 (AP-2). Scientific reports concerning their function in carcinogenesis depend on particular family member and/or tumor type which proves the issue to be unsolved. Therefore, the present study examines role of the best-described AP-2 representatives, AP-2α and AP-2γ, through ontological analysis of their target genes and investigation what processes are differentially regulated in 21 cancers using samples deposited in Genomic Data Analysis Center (GDAC) Firehose. Methods Expression data with clinical annotation was collected from TCGA-dedicated repository GDAC Firehose. Transcription factor targets were obtained from Gene Transcription Regulation Database (GTRD), TRANScription FACtor database (TRANSFAC) and Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST). Monocle3 R package was used for global samples profiling while Protein ANalysis THrough Evolutionary Relationships (PANTHER) tool was used to perform gene ontology analysis. Results With RNA-seq data and Monocle3 or PANTHER tools we outlined differences in many processes and signaling pathways, separating tumor from normal tissues or tumors from each other. Unexpectedly, a number of alterations in basal-like breast cancer were identified that distinguished it from other subtypes, which could bring future clinical benefits. Conclusions Our findings indicate that while the AP-2α/γ role remains ambiguous, their activity is based on processes that underlie the cancer hallmarks and their expression could have potential in diagnosis of selected tumors.

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Section: Introductionsupporting

confidence: 64%

Functional genomics of AP-2α and AP-2γ in cancers: in silico study

et al. 2020

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“…κ-carrageenan and glycerol were obtained from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China) Polyoxometalate (K 6 [Mo 18 O 62 P]) were synthesized according to the previous literature [ 25 ]. Escherichia coli ( E. coli ) and Staphylococcus aureusin ( S. aureus ) were purchased from China of Industrial Culture Collection (Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

Preparation and Characterization of Biodegradable κ-Carrageenan Based Anti-Bacterial Film Functionalized with Wells-Dawson Polyoxometalate

Zhou

Wang²,

Zhang³

et al. 2022

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In the present study, an anti-bacterial film (Carr/POM film) was prepared through the incorporation of Wells-Dawson polyoxometalate K6[Mo18O62P2] into κ-carrageenan-based polymers using the tape-casting method. The mechanical properties, thermal stability, and morphology of the prepared film were characterized. The obtained results showed that incorporation of K6[Mo18O62P2] significantly affected the morphology and structure of the films. Moreover, the polyoxometalate-based film demonstrated desirable bactericidal activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive). Carr/POM (@8 mg/mL) film resulted in an obvious inhibition zone around the film in Kirby-Bauer disk diffusion test, which could also remove 99% of S. aureus and E. coli on plastic, glass, and stainless steel. In addition, this anti-bacterial film also demonstrated good biodegradability, which could be decomposed in soil in around 1 week. In conclusion, the polyoxometalate-based film showed good anti-bacterial property against food-borne pathogenic microbes, suggesting the prepared film has great potential to be developed as promising food packaging.

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“…Recently, we examined the role of WWOX in conjunction with two interacting proteins, which together orchestrated biological processes diversely in BLCA depending on their cellular level [8]. These were two Activating Enhancer-Binding Protein 2 (AP-2) Transcription Factors (TFs), AP-2α and AP-2γ, members of the AP-2 family, whose natural function is related to early development regulation [9], but which are also involved in carcinogenesis [10][11][12][13][14], including BLCA [15][16][17]. AP-2α and AP-2γ have distinct roles in different tumors, and tend to play an anti-cancer or tumor-promoting role, respectively [9].…”

Section: Introductionmentioning

confidence: 99%

WWOX Loses the Ability to Regulate Oncogenic AP-2γ and Synergizes with Tumor Suppressor AP-2α in High-Grade Bladder Cancer

Kołat

Kałuzińska

Płuciennik

2021

Cancers

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The cytogenic locus of the WWOX gene overlaps with the second most active fragile site, FRA16D, which is present at a higher frequency in bladder cancer (BLCA) patients with smoking habit, a known risk factor of this tumor. Recently, we demonstrated the relevance of the role of WWOX in grade 2 BLCA in collaboration with two AP-2 transcription factors whose molecular actions supported or opposed pro-cancerous events, suggesting a distinct character. As further research is needed on higher grades, the aim of the present study was to examine WWOX-AP-2 functionality in grade 3 and 4 BLCA using equivalent in vitro methodology with additional transcriptome profiling of cellular variants. WWOX and AP-2α demonstrated similar anti-cancer functionality in most biological processes with subtle differences in MMP-2/9 regulation; this contradicted that of AP-2γ, whose actions potentiated cancer progression. Simultaneous overexpression of WWOX and AP-2α/AP-2γ revealed that single discrepancies appear in WWOX-AP-2α collaboration but only at the highest BLCA grade; WWOX-AP-2α collaboration was considered anti-cancer. However, WWOX only appeared to have residual activity against oncogenic AP-2γ in grade 3 and 4: variants with either AP-2γ overexpression alone or combined WWOX and AP-2γ overexpression demonstrated similar pro-tumoral behavior. Transcriptome profiling with further gene ontology certified biological processes investigated in vitro and indicated groups of genes consisting of AP-2 targets and molecules worth investigation as biomarkers. In conclusion, tumor suppressor synergism between WWOX and AP-2α is unimpaired in high-grade BLCA compared to intermediate grade, yet the ability of WWOX to guide oncogenic AP-2γ is almost completely lost.

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Identification of a Wells–Dawson polyoxometalate-based AP-2γ inhibitor with pro-apoptotic activity

Cited by 9 publications

References 52 publications

Functional genomics of AP-2α and AP-2γ in cancers: in silico study

Functional genomics of AP-2α and AP-2γ in cancers: in silico study

Preparation and Characterization of Biodegradable κ-Carrageenan Based Anti-Bacterial Film Functionalized with Wells-Dawson Polyoxometalate

WWOX Loses the Ability to Regulate Oncogenic AP-2γ and Synergizes with Tumor Suppressor AP-2α in High-Grade Bladder Cancer

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