Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote
treatment resistance,,–. This phenomenon has been implicated in chemorefractory small cell
lung cancer and resistance to targeted therapies,,–, but remains incompletely defined. Here,
we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune
signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences
(SPARCS) are oriented inversely in 3′ untranslated regions of specific genes enriched for …

Introduction: Tumor cell heterogeneity is a key determinant of cancer progression and drug
resistance, which is often mediated by mesenchymal cell subpopulations. While these
subclones can secrete growth factors, chemokines and cytokines, the immune signaling
networks that fuel this pro-tumorigenic state remain incompletely defined. Elucidating what
underlies this state would provide insights into tumor biology and inform clinical strategies to
improve anti-cancer therapies. Methods: Because of their well-defined nature, we used the …