KDF1 Promoted Proliferation and Metastasis of Epithelial Ovarian Cancer via Wnt/Beta-Catenin Pathway: TCGA-Based Data Mining and Experimental Validation

Zhu, Changyu; Liu, Yilong; Tong, Rongsheng; Guan, Jianmei

doi:10.3389/fgene.2022.808100

Cited by 7 publications

(6 citation statements)

References 33 publications

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“…Quite different from the role observed in epidermal progenitor cells and ccRCC cells [6], KDF1 was found to promote rather than inhibit the proliferation of epithelial ovarian cancer cells [7] and LUAD cells in a study of Zhu et al and our present study, respectively. This phenomenon may be explained by the molecular function of KDF1 as a scaffold, adaptor or cofactor, since different cellular contexts may mean different molecular partners present that interact with KDF1.…”

Section: Discussioncontrasting

confidence: 99%

“…In a previous study, we observed that KDF1 was downregulated in clear cell renal cell carcinoma and might act as a suppressing factor in the disease [6]. In contrast, KDF1 was reported to play an oncogenic role in epithelial ovarian cancer recently [7]. Based on these studies, KDF1 may not play a single regulatory role in the carcinogenesis process.…”

Section: Introductionmentioning

confidence: 95%

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KDF1 Promoted Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells through Activating STAT3 and AKT Pathway

Guo,

Gan,

Bao

et al. 2023

Biomedicines

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KDF1 has been reported to be correlated with carcinogenesis. However, its role and mechanism are far from clear. To explore the possible role and underlying mechanism of KDF1 in lung adenocarcinoma (LUAD), we investigated KDF1 expression in LUAD tissues and the influence of KDF1 in the phenotype of LUAD cells (A549 and PC-9) as well as the underlying mechanism. Compared to non-tumor lung epithelial cells, KDF1 was upregulated in the cancer cells of the majority of LUAD patients, and its expression was correlated with tumor size. Patients with enhanced KDF1 in cancer cells (compared with paired adjacent non-neoplastic lung epithelial cells) had shorter overall survival than patients with no increased KDF1 in cancer cells. Knockdown of KDF1 inhibited the migration, proliferation and invasion of LUAD cells in vitro. And overexpression of KDF1 increased the growth of the subcutaneous tumors in mice. In terms of molecular mechanisms, overexpression of KDF1 induced the expression of AKT, p-AKT and p-STAT3. In KDF1-overexpressing A549 cells, inhibition of the STAT3 pathway decreased the level of AKT and p-AKT, whereas inhibition of the AKT pathway had no effect on the activation of STAT3. Inhibition of STAT3 or AKT pathways reversed the promoting effects of KDF1 overexpression on the LUAD cell phenotype and STAT3 inhibition appeared to have a better effect. Finally, in the cancer cells of LUAD tumor samples, the KDF1 level was observed to correlate positively with the level of p-STAT3. All these findings suggest that KDF1, which activates STAT3 and the downstream AKT pathway in LUAD, acts as a tumor-promoting factor and may represent a therapeutic target.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 95%

KDF1 Promoted Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells through Activating STAT3 and AKT Pathway

Guo,

Gan,

Bao

et al. 2023

Biomedicines

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“…A recent report indicated that KDF1 activates the Wnt/β-catenin pathway, an important regulator of tooth and epithelial-mesenchymal interactions [ 25 ]. The impact of KDF1 variants on Wnt signaling activity was evaluated using the TOP-flash/FOP-flash luciferase reporter system.…”

Section: Resultsmentioning

confidence: 99%

“…The early epithelial signaling centers are mediated by four popular signaling pathways, Wnt, BMP, FGF, and Shh, and these pathways are particularly significant for primary enamel knot budding, which further determines tooth crown morphogenesis and late enamel formation [ 29 , 32 , 33 , 34 , 35 , 36 , 37 ]. A recent study demonstrated that KDF1 can activate the Wnt signaling pathway to regulate the epithelial-to-mesenchymal transition process in ovarian cancer [ 25 ]. Our results from Wnt luciferase assessments demonstrated that the novel KDF1 R307P variant and the other three reported variants suppressed Wnt signaling activation, suggesting that the loss-of-function of the variant allele might be the pathogenic mechanism of KDF1 variation in tooth agenesis.…”

Section: Discussionmentioning

confidence: 99%

KDF1 Novel Variant Causes Unique Dental and Oral Epithelial Defects

Liu

et al. 2022

IJMS

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Keratinocyte differentiation factor 1 (KDF1) is a recently identified and rare candidate gene for human tooth agenesis; however, KDF1-related morphological characteristics and pathological changes in dental tissue and the oral epithelium remain largely unknown. Here, we employed whole-exome sequencing (WES) and Sanger sequencing to screen for the suspected variants in a cohort of 151 tooth agenesis patients, and we segregated a novel KDF1 heterozygous missense variation, c.920G>C (p.R307P), in a non-syndromic tooth agenesis family. Essential bioinformatics analyses and tertiary structural predictions were performed to analyze the structural changes and functional impacts of the novel KDF1 variant. The subsequent functional assessment using a TOP-flash/FOP-flash luciferase reporter system demonstrated that KDF1 variants suppressed the activation of canonical Wnt signaling in 293T cells. To comprehensively investigate the KDF1-related oral morphological anomalies, we performed scanning electron microscopy and ground section of the lower right lateral deciduous incisor extracted from #285 proband, and histopathological assessment of the gingiva. The phenotypic analyses revealed a series of tooth morphological anomalies related to the KDF1 variant R307P, including a shovel-shaped lingual surface of incisors and cornicione-shaped marginal ridges with anomalous morphological occlusal grooves of premolars and molars. Notably, keratinized gingival epithelium abnormalities were revealed in the proband and characterized by epithelial dyskeratosis with residual nuclei, indistinct stratum granulosum, epithelial hyperproliferation, and impaired epithelial differentiation. Our findings revealed new developmental anomalies in the tooth and gingival epithelium of a non-syndromic tooth agenesis individual with a novel pathogenic KDF1 variant, broadening the phenotypic spectrum of KDF1-related disorders and providing new evidence for the crucial role of KDF1 in regulating human dental and oral epithelial development.

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“…Current diagnosis of OC relies on the International Federation of Gynecology and Obstetrics (FIGO) stage system and serum biomarkers [3,4]. It has been found that these markers are not ideal for precisely predicting a patient's prognosis and curative effects [5][6][7]. Most patients with OC are diagnosed at an advanced stage [8].…”

Section: Introductionmentioning

confidence: 99%

Low expression of ACOT13 predicts poor prognosis and immunotherapy outcome in ovarian cancer

Xie

2024

Am J Transl Res

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Objective: Acyl-CoA thioesterase 13 (ACOT13) is involved in lipid biosynthesis, gene transcription, and signal transduction. We explored the potential of ACOT13 to predict ovarian cancer (OC) prognosis and patient immunotherapy responses. Methods: The Cancer Genome Atlas and Gene Expression Omnibus databases were used to extract raw data. To investigate the potential of ACOT13 as a prognostic and immunotherapeutic marker for OC, bioinformatic analyses were performed using the TIMER website, LinkedOmics database, and R software. We also explored the effects on the invasive ability of OC cells in vitro using a ACOT13 knockdown. Results: The expression of ACOT13 in OC was high and associated with a better prognosis. The expression of ACOT13 was also linked to immune cell invasion immunity-related gene expression. Additionally, immunotherapy was more effective in patients with high ACOT13 expression levels. Multiple critical signaling pathways were found to be involved in the role of ACOT13 in energy metabolism and cell mobility based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. OC cells invaded and migrated significantly more when ACOT13 was knocked down. Conclusion: High ACOT13 expression in OC is associated to a better OC outcome.

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KDF1 Promoted Proliferation and Metastasis of Epithelial Ovarian Cancer via Wnt/Beta-Catenin Pathway: TCGA-Based Data Mining and Experimental Validation

Cited by 7 publications

References 33 publications

KDF1 Promoted Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells through Activating STAT3 and AKT Pathway

KDF1 Promoted Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells through Activating STAT3 and AKT Pathway

KDF1 Novel Variant Causes Unique Dental and Oral Epithelial Defects

Low expression of ACOT13 predicts poor prognosis and immunotherapy outcome in ovarian cancer

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