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Saccà et al. J Cancer Metastasis Treat 2019;5:15 I http://dx.doi.org/10.20517/2394-4722.2018.95 Page 7 of 9

A

B

Figure 4. Non-histone lysine specific demethylase 1 (LSD1) substrate: hypoxia inducible factor-1 alpha (HIF-1α) protein stability is
modulated by LSD1. A: Metylation-demethylation by SET7/9 and LSD1 respectively regulates HIF-1α degradation; B: LSD1-mediated
regulation of HIF-1α protein stability during hypoxia: In early stage of hypoxia, the LSD1 (FAD-dependent) demethylase activity protects
HIF-1α from RACK1-mediated degradation and HIF-1α activates transcription of its target genes. In prolonged hypoxia, the absence of
FAD impairs FAD-dependent LSD1 activity on HIF-1α with consequent RACK1-dependent HIF-1α protein degradation

the inhibition of chemokine receptors, by combined treatment with PD-1 antibody and LSD1 inhibitors,
[58]
suppresses tumor growth and metastasis .
In conclusion, LSD1 inhibitors represent a promising epigenetic approach to treat breast Cancer.
Furthermore, for a possible therapeutic goal, developing new drugs that target LSD1 and its partners or
immune modulators would carry high innovation and translational potential.

DECLARATIONS
Authors’ contributions
All authors partecipated in drafting the article and to its critical revision and approved the final version to be
published.

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by grants from AIRC (I.G. 13173).

Conflicts of interest
All authors declared that there are no conflicts of interest.