BRD4S-LOXL2 nuclear interaction promotes breast cancer


BRD4S-LOXL2 nuclear interaction promotes breast cancer

Our lab at the Centre for Genomic Regulation together with collaborators from the Vall d’Hebron Institute of Oncology has made an important discovery that could lead to new treatments for triple-negative breast cancer. This aggressive form of breast cancer lacks the receptors targeted by current drugs and has a poor prognosis.

We found that the enzyme LOXL2 drives the growth of triple-negative breast cancer cells. Further analyses showed LOXL2 expression predicts the effectiveness of drugs targeting the cancer-promoting protein BRD4. This suggested LOXL2 and BRD4 might interact to promote cancer growth. We demonstrated that LOXL2 binds to BRD4 in the nucleus, altering gene expression in a way that spurs triple-negative breast cancer cell growth. Simultaneously inhibiting both proteins disrupted their interactions and slowed cancer growth in cell cultures and mouse models.

Our findings reveal a new mechanism driving triple-negative breast cancer that can potentially be targeted for treatment. A dual-inhibitor strategy against LOXL2 and BRD4 could make triple-negative breast cancer more treatable when combined with other therapies.

More work is needed before patients benefit from our discovery. But progress in understanding this aggressive cancer’s growth mechanisms is encouraging. As we continue shedding light on triple-negative breast cancer biology, its health challenges may become more surmountable than previously thought.

Our results have implications for BET inhibitors – experimental drugs targeting BRD4 that have shown promise against triple-negative breast cancer but failed clinical trials due to resistance. We believe simultaneously inhibiting LOXL2 could help overcome this resistance.

Read the original publication at EMBO Molecular Medicine.

Read the CRG/VHIO press release in English, Spanish or Catalan.

A cool painting depiction of the project, which unfortunatley did not get selected for the cover. Credits to Mariangela Corsetti.

Sdelci Lab