The MYB-related transcription factor MYPOP acts as a selective regulator of cancer cell growth

The MYB-related transcription factor and partner of profilin (MYPOP or p42POP) is a ubiquitously expressed and understudied protein, recently discovered in restricting oncogenic human papillomaviruses (HPV) and suggested as a tumor suppressor. In this study, we investigate the role of MYPOP on cancer cells. At supra-physiological levels, induced by both plasmid DNA- and messenger RNA-mediated gene transfer, MYPOP emerges as a potent tumor growth inhibitor, capable of inducing cancer cell death while sparing normal cells. Using HPV-transformed cervical cancer cells and normal human epidermal keratinocytes, cell behavior assessments as well as transcriptome analysis revealed MYPOP's specific anti-proliferative and death-inducing impact on cancer cells. We found MYPOP capable of silencing viral and human oncogenes including E6 , E7 , and MYC , and of triggering the release of the cancer-killing cytokine interleukin-24. Extending our research to murine Mypop, we observed anti-proliferative effects in mouse melanoma and colorectal cancer cells. Collectively, our findings underscore MYPOP's potential as a selective tumor suppressor in both human and mouse cancer cells, opening a promising avenue for future in vivo studies.