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Abstract

Cell senescence suppresses tumors by arresting cells at risk of becoming malignant. However, this process in turn can affect the microenvironment, leading to acquisition of a senescence-associated secretory phenotype (SASP) that renders senescent cells proinflammatory and results in tumor progression. But how is SASP controlled? In this issue of the JCI, Attig and Pape et al. describe the role of chimeric calbindin 1 (CALB1) transcripts, which are driven by an upstream human endogenous retrovirus subfamily H (HERVH) element. The authors propose that in lung squamous cell carcinoma (LUSC), HERVH-driven isoforms of calbindin (HERVH-CALB1) counteract SASP. As an alternative promoter, HERVH drove calbindin isoforms that prevented cancer cell senescence and associated inflammation, which was associated with better patient survival. We comment on the similarities between HERVH-CALB1–related cellular fitness in cancer and early embryogenesis and discuss the potential benefits of HERVH-driven chimeric transcripts.