Prognostic value of plasma levels of HIF-1a and PGC-1a in breast cancer

Cai, Fengfeng; Xu, Cheng; Pan, Xin; Cai, Lei; Lin, Xinhua; Su, Chen; Biskup, Ewelina

doi:10.18632/oncotarget.12796

Cited by 45 publications

(39 citation statements)

References 54 publications

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“…An increased reliance on OXPHOS with a marked shift away from aerobic glycolysis was observed in glioma stem cells [ 40 ]. Similarly, high PGC1α and HIF1α levels have been suggested as effective and non-invasive plasma biomarkers of poor prognosis for patient with breast cancer [ 41 ]. The findings of the present study support a role for PGC1α in the regulation of oncogenic properties.…”

Section: Discussionmentioning

confidence: 99%

PGC1α induced by reactive oxygen species contributes to chemoresistance of ovarian cancer cells

Kim

Jung

et al. 2017

Oncotarget

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Malignant cells are subjected to high levels of oxidative stress that arise from the increased production of reactive oxygen species (ROS) due to their altered metabolism. They activate antioxidant mechanisms to relieve the oxidative stress, and thereby acquire resistance to chemotherapeutic agents. In the present study, we found that PGC1α, a key molecule that both increases mitochondrial biogenesis and activates antioxidant enzymes, enhances chemoresistance in response to ROS generated by exposure of cells to ovarian sphere-forming culture conditions. Cells in the cultured spheres exhibited stem cell-like characteristics, and maintained higher ROS levels than their parent cells. Intriguingly, scavenging ROS diminished the aldehyde dehydrogenase (ALDH)-positive cell population, and inhibited proliferation of the spheres. ROS production triggered PGC1α expression, which in turn caused changes to mitochondrial biogenesis and activity within the spheres. The drug-resistant phenotype was observed in both spheres and PGC1α-overexpressing parent cells, and conversely, PGC1α knockdown sensitized the spheres to cisplatin treatment. Similarly, floating malignant cells derived from patient ascitic fluid included an ALDH-positive population and exhibited the tendency of a positive correlation between expressions of multidrug resistance protein 1 (MDR1) and PGC1α. The present study suggests that ROS-induced PGC1α mediates chemoresistance, and represents a novel therapeutic target to overcome chemoresistance in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

PGC1α induced by reactive oxygen species contributes to chemoresistance of ovarian cancer cells

Kim

Jung

et al. 2017

Oncotarget

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“…It has been demonstrated that HIF1-α overexpression was detected in a variety of solid tumors (20). Meanwhile, recent studies have shown that in oral squamous cell carcinoma (21), esophageal squamous cell carcinoma (22), renal clear cell carcinoma (23) and breast cancer (24), HIF1-α expression was correlated with cancer metastasis. In our study, we demonstrated that 57 cases of 103 samples were HIF1-α-positive, and consistent with previous findings (25), HIF1-α levels were associated with BMPR2, bone morphogenetic protein receptor 2; HIF1-α, hypoxia-inducible factor 1-α; ROC, receiver operating characteristics; 95% CI, 95% confident interval; +, positive; -, negative; † , included BMPR2+HIF1-α-, BMPR2-HIF1-α+, and BMPR2-HIF1-α-.…”

Section: Discussionmentioning

confidence: 99%

BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival

Wang

Ren

Huang

et al. 2017

Chinese Journal of Cancer Research

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Objective: Bone morphogenetic protein receptor 2 (BMPR2) and hypoxia-inducible factor 1-α (HIF1-α) existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown. Methods:To investigate the clinical significance of BMPR2 and HIF1-α in osteosarcoma, we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry. Meanwhile, we conducted a follow-up to examine the metastatic behavior and overall survival (OS) of osteosarcoma patients.Results: Among 103 tissues, 61 cases had BMPR2-positive expression and 57 cases had HIF1-α positive expression. A significant correlation was noticed between BMPR2 and HIF1-α expression in osteosarcoma specimens (P=0.035). Receiver-operating characteristic (ROC) curves were calculated to investigate the predictive value of the two markers in tumor metastasis. By means of univariate and multivariate analysis, BMPR2 and HIF1-α expression, as well as higher tumor grade, were identified as significant risk factors for OS in patients with osteosarcoma. Kaplan-Meier survival analysis revealed that the patients with BMPR2 and HIF1-α positive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative staining.Conclusions: It can be concluded that BMPR2 and HIF1-α expression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.

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“…Breast cancer patients exhibit significantly high HIF-1α levels, which correlate with more aggressive cancer features, and particularly with a poor disease free and overall survival 52 . Our results showed that HT (50-200 µM) decreased HIF-1α protein level without modulating its mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between hydroxytyrosol, a major olive oil phenol, and HIF-1 in MCF-7 breast cancer cells

Calahorra

Martı́nez-Lara

Granadino‐Roldán

et al. 2020

Sci Rep

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Olive oil intake has been linked with a lower incidence of breast cancer. Hypoxic microenvironment in solid tumors, such as breast cancer, is known to play a crucial role in cancer progression and in the failure of anticancer treatments. HIF-1 is the foremost effector in hypoxic response, and given that hydroxytyrosol (HT) is one of the main bioactive compounds in olive oil, in this study we deepen into its modulatory role on HIF-1. Our results in MCF-7 breast cancer cells demonstrate that HT decreases HIF-1α protein, probably by downregulating oxidative stress and by inhibiting the PI3K/ Akt/mTOR pathway. Strikingly, the expression of HIF-1 target genes does not show a parallel decrease. Particularly, adrenomedullin and vascular endothelial growth factor are up-regulated by high concentrations of HT even in HIF-1α silenced cells, pointing to HIF-1-independent mechanisms of regulation. In fact, we show, by in silico modelling and transcriptional analysis, that high doses of HT may act as an agonist of the aryl hydrocarbon receptor favoring the induction of these angiogenic genes. In conclusion, we suggest that the effect of HT in a hypoxic environment is largely affected by its concentration and involves both HIF-1 dependent and independent mechanisms.

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Prognostic value of plasma levels of HIF-1a and PGC-1a in breast cancer

Cited by 45 publications

References 54 publications

PGC1α induced by reactive oxygen species contributes to chemoresistance of ovarian cancer cells

PGC1α induced by reactive oxygen species contributes to chemoresistance of ovarian cancer cells

BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival

Crosstalk between hydroxytyrosol, a major olive oil phenol, and HIF-1 in MCF-7 breast cancer cells

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