Breast cancer is the most common cancer in women globally, with triple-negative breast cancer (TNBC) standing out as its most aggressive and deadly form. Known for its high recurrence rates and tendency to spread to the lungs after surgery, TNBC drastically reduces patient survival and quality of life. While metabolic changes in cancer cells have been linked to tumor progression, the exact mechanisms remain unclear.
A recent study has pinpointed lysophosphatidylcholine acyltransferase 1 (LPCAT1), an enzyme highly active in TNBC and lung metastases, as a critical culprit. LPCAT1 fuels cancer aggression by boosting cellular energy (ATP) levels, which in turn activates the TGFβ signaling pathway—a known driver of tumor growth and spread. This process relies on ATP-dependent genetic reprogramming orchestrated by the BAF protein complex, with DPF2 playing a central role. Together, the LPCAT1-DPF2-TGFBR2 axis supercharges TNBC’s malignant behavior.
To combat this, researchers designed a breakthrough therapy: tiny, reduction-responsive nanoparticles that deliver LPCAT1-targeted siRNA (siLPCAT1) directly into cancer cells. In preclinical tests, this approach effectively silenced LPCAT1, starving tumors of their energy supply and dramatically reducing both tumor growth and lung metastasis.
“Our findings reveal LPCAT1 as a linchpin in TNBC’s deadly spread and offer a precision nanotherapy to dismantle it,” said the research team. This strategy could fill a critical gap in treating advanced TNBC, where current options are limited. Future work will focus on translating these results into clinical trials.
The study underscores the potential of targeting cancer metabolism with nanotechnology, opening new doors for combating aggressive breast cancer.
Science China Life Sciences
Experimental study