Although it remains to be determined, given that a131 treatment or PIP4Ks knockdown also arrested normal cells at the G1/S phase, it is tempting to speculate that a131 treatment or PIP4Ks knockdown may increase PI(5)P levels to activate a nuclear receptor that promotes transcriptional upregulation of PIK3IP1. Conversely, activated Ras may signal to inhibit such nuclear receptors or transcription factors to suppress PIK3IP1 expression, thereby establishing positive cross-talk with the PI3K pathway in Ras-pathway mutated/activated cancers for proliferation. The gene discussed is SERPINB5; the disease is cancer.