Keratin 5 expression defines a niche-supported hierarchy in tubo-ovarian cancer

Tubo-ovarian high-grade serous carcinoma (HGSC) is characterized by extreme cellular heterogeneity. A tumorigenic subset of cancer-propagating cells (CPC) with stem-like properties coexists with a large population of non-cancer-propagating cells (non-CPC), but the functional interplay between these two cell types remains poorly understood. In this issue, Bidarimath et al. identify keratin 5 (KRT5) as a marker of CPC in HGSC and propose a niche model in which osteopontin (OPN) sustains KRT5-positive CPC through interactions with KRT5-negative, non-tumorigenic cells. By combining in vitro, in vivo, and patient-derived data, the study links a supportive tumor microenvironment to the maintenance of a phenotypically defined CPC population.