SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors

@article{Montagner2012SHARP1SB,
  title={SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors},
  author={Marco Montagner and Elena Enzo and Mattia Forcato and Francesca Zanconato and Anna Rosita Parenti and {\'E}. F. Rampazzo and Giuseppe Basso and Genesio Leo and Antonio Rosato and Silvio Bicciato and Michelangelo Cordenonsi and Stefano Piccolo},
  journal={Nature},
  year={2012},
  volume={487},
  pages={380-384}
}
The molecular determinants of malignant cell behaviours in breast cancer remain only partially understood. Here we show that SHARP1 (also known as BHLHE41 or DEC2) is a crucial regulator of the invasive and metastatic phenotype in triple-negative breast cancer (TNBC), one of the most aggressive types of breast cancer. SHARP1 is regulated by the p63 metastasis suppressor and inhibits TNBC aggressiveness through inhibition of hypoxia-inducible factor 1α (HIF-1α) and HIF-2α (HIFs). SHARP1 opposes… 
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References

SHOWING 1-10 OF 34 REFERENCES
Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation
TLDR
It is demonstrated that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOx-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment.
Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics
TLDR
This review summarizes the current state of knowledge regarding the molecular mechanisms by which Hif-1 contributes to cancer progression, focusing on clinical data associating increased HIF-1 levels with patient mortality and pharmacological data showing anticancer effects of H IF-1 inhibitors in mouse models of human cancer.
Hypoxia-inducible factor-2alpha correlates to distant recurrence and poor outcome in invasive breast cancer.
TLDR
It was shown that although HIF-1alpha and Hif-2alpha protein levels in breast cancer specimens were not interrelated, high levels of both HAFs were associated to high VEGF expression, which was an independent prognostic factor associated to reduced recurrence-free and breast cancer-specific survival.
Differential prognostic impact of hypoxia induced and diffuse HIF-1α expression in invasive breast cancer
TLDR
Investigating the prognostic impact of different HIF-1α overexpression patterns in relation to its downstream effectors carbonic anhydrase (CA) IX and glucose transporter 1 (GLUT-1) found patients with diffuse Hif-1 α staining had a significantly better prognosis than patients with perinecrotically overexpressed HIF -1α.
TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs
TLDR
A novel understanding of the roles of TAp63 in tumour and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR-130b is provided and may have implications for the many processes regulated by miRNAs.
Constitutive/Hypoxic Degradation of HIF-α Proteins by the Proteasome Is Independent of von Hippel Lindau Protein Ubiquitylation and the Transactivation Activity of the Protein*
TLDR
A constitutive, ubiquitin-independent proteasomal degradation pathway of HIF-α proteins has to be taken into account in understanding the biology as well as in the development of therapeutic interventions of highly hypoxic tumors.
...
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