Cardamonin inhibited growth of the triple negative breast cancer cell line MDA-MB-231 in vitro and in vivo by suppressing HIF-1α mediated cell metabolism.
The Milk Protein Alpha-Casein Suppresses Triple Negative Breast Cancer Stem Cell Activity Via STAT and HIF-1alpha Signalling Pathways in Breast Cancer Cells and Fibroblasts.
To elucidate the role of the mammalian target of rapamycin (mTOR) signaling pathway in TNBC, the expression of molecules involved in mTOR signaling including mTOR, phosphorylated (p)-mTOR, p-4EBP1, GLUT1, GLUT3, HIF-1α, and Ki67 was investigated by immunohistochemistry in 35 TNBC and 81 non-TNBC cases.
Previous studies have revealed that long intergenic non-coding RNA for kinase activation (LINK-A), a long non-coding RNA (lncRNA) promotes disease progression in triple-negative breast cancer by activating hypoxia-inducible factor 1α (HIF1α).
The protein level of HIF-1α remains largely unchanged in cultured TNBC cells and xenografts, partially due to its upregulated transcription by vitamin C, suggesting that HIF-1α unlikely mediates the action of vitamin C on metastasis.
For improving the therapeutic efficacy of TNBC, we developed a new kind of multifunctional cationic porphyrin-grafted lipid (CPGL) microbubble loaded with HIF 1α siRNA (siHIF@CpMB).
Bioinformatic analysis further indicated a mechanism by which HIF-1α can regulate ST3GAL6 expression and the relationship within the intrinsic characteristics of TNBC tumors.
These surprising results delineate a mechanism by which a transcription factor switches cells from ERK to p38 signaling in response to chemotherapy and suggest that therapeutic targeting of HIF1 or the p38 pathway in combination with chemotherapy will block BCSC enrichment and improve outcome in TNBC.<b>Significance:</b> These findings provide a molecular mechanism that may account for the increased relapse rate of women with TNBC who are treated with cytotoxic chemotherapy and suggest that combining chemotherapy with an inhibitor of HIF1 or p38 activity may increase patient survival.<i></i>.
Psammaplin-based histone deacetylase (HDAC) inhibitors were found to differentially inhibit HDAC activity, induce activation of hypoxia-inducible factor-1 (HIF-1), and disrupt organotropic metastatic TNBC subclone growth.
These data suggest that (1) MYC and MCL1 confer resistance to chemotherapy by expanding CSCs via mtOXPHOS and (2) targeting mitochondrial respiration and HIF-1α may reverse chemotherapy resistance in TNBC.
Levels of HIF-1α and stem cells in the tumor were quantitated by Western blotting and flow cytometry.<b>Results:</b> The magnitude (<i>P</i> < 0.001) and incidence (<i>P</i> < 0.001) of HIF-1α-specific IgG were elevated in TNBC patients compared with controls.
The suppression of IL-6 by G-1 can further inhibit HIF-1α and STAT3 signals in TNBC cells by inhibition their expression, phosphorylation and/or nuclear localization.
In summary, multiple cycles of hypoxia and reoxygenation have a more pronounced effect on the promotion of TNBC invasiveness than CH; HIF-1α activation and downstream vimentin upregulation may account for this phenotypic change.
Our study suggests a tumor-suppressive function of PRC2, which is restricted by HIF1-α, and an oncogenic function of Ezh2, which cooperates with FoxM1 to promote invasion in triple-negative breast cancer.
Immunohistochemical staining for HIF1α and CAIX was performed to determine the correlation with clinicopathologic variables and survival outcome on tissue microarrays from 270 early-stage TNBC patients.
These results suggest that, in combination with chemotherapy, targeting BCSCs by inhibiting HIF-1-regulated glutathione synthesis may improve outcome in TNBC.
Expression of HIF-1α and Markers of Angiogenesis Are Not Significantly Different in Triple Negative Breast Cancer Compared to Other Breast Cancer Molecular Subtypes: Implications for Future Therapy.
In conclusion, the recombinant lentivirus containing HIF-1α siRNA provides a new avenue for developing novel therapy for triple negative breast cancer.
Treatment of TNBC cell lines with dutasteride was associated with a dose-dependent decrease in cell viability, altered protein expression of VEGF and HIF-1α and increased chemosensitivity.
Primary tumors of ganetespib-treated mice had significantly reduced levels of HIF-1α (but not HIF-2α) protein and of HIF-1 target gene mRNAs encoding proteins that play key roles in angiogenesis, metabolism, invasion, and metastasis, thereby providing a molecular basis for observed effects of the drug on the growth and metastasis of triple-negative breast cancer.
Analysis of independent cohorts of patients with TNBC revealed a specific XBP1 gene expression signature that was highly correlated with HIF1α and hypoxia-driven signatures and that strongly associated with poor prognosis.