To further explore differentiation in vitro, we cultured H1299 spheroids on basement membrane matrix (Matrigel) and found that while H1299control spheroids maintained rounded morphology, associated with cancer stem cell phenotype (Yu et al, 2017), RASSF1A‐expressing H1299 spheroids collapsed and formed branched structures reminiscent of a differentiated epithelium (Fig 7D, Movie EV3). The gene discussed is RASSF1; the disease is cancer.