Protein DNM1 Identified as Key Regulator in Ovarian Cancer Metastasis

Recent groundbreaking research has uncovered the critical role of the protein DNM1 in driving the spread of ovarian cancer, the most lethal cancer affecting women’s reproductive health. Ovarian cancer is notorious for being difficult to treat once it metastasizes beyond the ovaries, which underscores the importance of understanding the underlying mechanisms that facilitate its progression.

A study published in the journal Protein & Cell and led by Professor Alice Wong from The University of Hong Kong utilized advanced gene and protein network analysis across over 8,000 patient samples from 20 different cancer types. The researchers employed a master regulator algorithm to identify key drivers of epithelial-to-mesenchymal transition (EMT), a biological process that enhances cancer cell mobility and invasiveness. Through this analysis, DNM1 emerged as a novel, non-transcriptional regulator influencing EMT, notably through its role in the endocytic recycling of N-cadherin, a protein essential for cell adhesion and movement.

Higher levels of DNM1 were observed in patients with advanced, mesenchymal subtype ovarian cancers, correlating with worse survival outcomes. Experimental studies demonstrated that inhibiting DNM1 in ovarian cancer cells significantly reduced their migratory capacity and lowered N-cadherin levels, thereby diminishing their metastatic potential. Conversely, increasing DNM1 levels made non-metastatic cells more invasive.

Further insights revealed that DNM1 facilitates cancer cell mobility by helping in the uptake and recycling of N-cadherin, processes vital for maintaining cell polarity and migratory ability. Importantly, non-metastatic cells showed increased expression of B3GALT1, which appears to inhibit EMT by reducing N-cadherin endocytosis. Interestingly, metastatic cells with high DNM1 levels were also more efficient at nanoparticle-based drug uptake, indicating potential for nanotherapy targeting.

These discoveries highlight the DNM1-N-cadherin axis as a key regulator of ovarian cancer metastasis and present a promising target for developing new therapeutic strategies. Targeting DNM1 could potentially thwart the metastatic spread, improving prognosis for patients with aggressive ovarian cancer.

This research advances our understanding of ovarian cancer biology and opens doors for innovative treatments aimed at halting disease progression by modulating DNM1 activity.