Novel cancer stem cell targets during epithelial to mesenchymal transition in PTEN-deficient trastuzumab-resistant breast cancer

Sun, Lichao; Burnett, Joseph; Gasparyan, Mari; Xu, Fangying; Jiang, Hui; Lin, Chang‐Ching; Myers, Ila; Korkaya, Hasan; Liu, Yajing; Connarn, Jamie; He, Huining; Zhang, Ning; Wicha, Max S.; Sun, Duxin

doi:10.18632/oncotarget.9839

Cited by 39 publications

(42 citation statements)

References 48 publications

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“…vinca alkaloids, taxanes, camptothecins [ 92 ] which have fewer side effects than synthetic ones. Recently, a new natural compound sulforaphane was identified, which eliminates cancer stem cells in many cancer types [ 93 – 95 ]. Multiple survival pathways make trouble for anticancer drug discovery.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of hypoxia-inducible factor and metabolic pathways: possible targets of cancer

Arora²,

et al. 2017

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Cancer, the main cause of human deaths in the modern world is a group of diseases. Anticancer drug discovery is a challenge for scientists because of involvement of multiple survival pathways of cancer cells. An extensive study on the regulation of each step of these pathways may help find a potential cancer target. Up-regulated HIF-1 expression and altered metabolic pathways are two classical characteristics of cancer. Oxygen-dependent (through pVHL, PHDs, calcium-mediated) and independent (through growth factor signaling pathway, mdm2 pathway, HSP90) regulation of HIF-1α leads to angiogenesis, metastasis, and cell survival. The two subunits of HIF-1 regulates in the same fashion through different mechanisms. HIF-1α translation upregulates via mammalian target of rapamycin and mitogen-activated protein kinase signaling pathways, whereas HIF-1β through calmodulin kinase. Further, the stabilized interactions of these two subunits are important for proper functioning. Also, metabolic pathways crucial for the formation of building blocks (pentose phosphate pathway) and energy generation (glycolysis, TCA cycle and catabolism of glutamine) are altered in cancer cells to protect them from oxidative stress and to meet the reduced oxygen and nutrient supply. Up-regulated anaerobic metabolism occurs through enhanced expression of hexokinase, phosphofructokinase, triosephosphate isomerase, glucose 6-phosphate dehydrogenase and down-regulation of aerobic metabolism via pyruvate dehydrogenase kinase and lactate dehydrogenase which compensate energy requirements along with high glucose intake. Controlled expression of these two pathways through their common intermediate may serve as potent cancer target in future.

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Section: Discussionmentioning

confidence: 99%

Overexpression of hypoxia-inducible factor and metabolic pathways: possible targets of cancer

Arora²,

et al. 2017

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“…Also, MEOX1 is related to signaling pathway. One study showed that HER2 signaling regulated MEOX1 in HER2 + breast cancer [9].Another report demonstrated that MEOX may control Bapx1 expression [20].…”

Section: Discussionmentioning

confidence: 99%

“…Besides, MEOX1 affected the progression of triple-negative breast cancer [7,8]. In addition, siRNA knockdown inhibits breast cancer cell frequency and the growth of tumor through down-regulation of MEOX1 [9]. However, the clinicopathological significance of MEOX1 in EEA remain unclear.…”

Section: Introductionmentioning

confidence: 99%

MEOX1 is a risk factor for unfavorable prognosis in human endometrioid endometrial adenocarcinoma

Liu

Dejun

Liu

et al. 2020

Preprint

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Background: Mesenchyme homeobox 1(MEOX1) is a homeobox transcription factor. Although MEOX1 has an impact on cancer, no studies investigated its expression in human endometrioid endometrial adenocarcinoma (EEA). This study aim to check the expression level of MEOX1 and detect its role in unfavorable prognosis. Methods: We used Western blot analysis by fresh frozen tissues and Immunohistochemical (IHC) method to detect the protein levels of MEOX1. Results: MEOX1 expression at the protein levels in EEA was gradually higher than that in normal group and benign hyperplastic endometrium group (both P < 0.001). The high expression of MEOX1 was correlated with depth of myometrial invasion, lymfpho-vascular space involvement, FIGO stage，lymph node metastasis and histological grade by univariate survival analysis. MEOX1 high-expression status in EEA was an independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS) by Multivariate survival analysis. Kaplan-Meier analysis demonstrated that MEOX1 expression was related to RFS and OS. Compared with the high expression MEOX1group,the low expression MEOX1 group had longer RFS and OS (both P < 0.001). Conclusion: MEOX1 may be a new potential biomarker for prognosis and recurrence in human EEA.

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“…Mutation in MEOX1 gene was involved in Klippel-Feil syndrome - a skeleton disease with abnormal fusion of two or more cervical vertebras [45]. In a recent study, MEOX1 was proved to be a key molecular target that regulating breast cancer stem cells and was associated with worse clinical survival in BC patients [46]. Given the information above, we infer that rs7808138 and rs4793019 are not only BMD GWAS-associated SNPs but also potential novel SNPs associated with BC.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer

et al. 2017

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Epidemiological and clinical evidences have shown that bone mineral density (BMD) has a close relationship with breast cancer (BC). They might potentially have a shared genetic basis. By incorporating information about these pleiotropic effects we may be able to explore more of the traits’ total heritability. We applied a recently developed conditional false discovery rate (cFDR) method to the summary statistics from two independent GWASs to identify the potential pleiotropic genetic variants for BMD and BC. By jointly analyzing two large independent GWASs of BMD and BC, we found strong pleiotropic enrichment between them and identified 102 single nucleotide polymorphisms (SNPs) in BMD and 192 SNPs in BC with cFDR < 0.05, including 230 SNPs that might have been overlooked by the standard GWAS analysis. cFDR-significant genes were enriched in GO terms and KEGG pathways which were crucial to bone metabolism and/or BC pathology (adjP<0.05). Some cFDR significant genes were partially validated in the gene expressional validation assay. Strong interactions were found between proteins produced by cFDR-significant genes in the context of biological mechanism of bone metabolism and/or BC etiology. Totally we identified 7 pleiotropic SNPs that were associated with both BMD and BC (conjunction cFDR<0.05), CCDC170, ESR1, RANKL, CPED1 and MEOX1 might play important roles in the pleiotropy of BMD and BC. Our study highlighted the significant pleiotropy between BMD and BC and shed novel insight into trait-specific as well as the potentially shared genetic architecture for both BMD and BC.

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Novel cancer stem cell targets during epithelial to mesenchymal transition in PTEN-deficient trastuzumab-resistant breast cancer

Cited by 39 publications

References 48 publications

Overexpression of hypoxia-inducible factor and metabolic pathways: possible targets of cancer

Overexpression of hypoxia-inducible factor and metabolic pathways: possible targets of cancer

MEOX1 is a risk factor for unfavorable prognosis in human endometrioid endometrial adenocarcinoma

Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer

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