YAP1 and PRDM14 converge to promote cell survival and tumorigenesis

Dev Cell. 2022 Jan 24;57(2):212-227.e8. doi: 10.1016/j.devcel.2021.12.006. Epub 2022 Jan 5.


The transcriptional co-activator YAP1 oncogene is the downstream effector of the Hippo pathway, which regulates tissue homeostasis, organ size, regeneration, and tumorigenesis. Multiple cancers are dependent on sustained expression of YAP1 for cell proliferation, survival, and tumorigenesis, but the molecular basis of this oncogene dependency is not well understood. To identify genes that can functionally substitute for YAP1, we performed a genome-scale genetic rescue screen in YAP1-dependent colon cancer cells expressing an inducible YAP1-specific shRNA. We found that the transcription factor PRDM14 rescued cell proliferation and tumorigenesis upon YAP1 suppression in YAP1-dependent cells, xenografts, and colon cancer organoids. YAP1 and PRDM14 individually activated the transcription of calmodulin 2 (CALM2) and a glucose transporter SLC2A1 upon YAP1 suppression, and CALM2 or SLC2A1 expression was required for the rescue of YAP1 suppression. Together, these findings implicate PRDM14-mediated transcriptional upregulation of CALM2 and SLC2A1 as key components of oncogenic YAP1 signaling and dependency.

Keywords: Hippo pathway; KRAS; PRDM14; YAP1; colon cancer; oncogene addiction; resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Calmodulin / genetics
  • Calmodulin / metabolism
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Colonic Neoplasms / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Glucose Transporter Type 1 / genetics
  • Humans
  • Mice
  • Mice, Nude
  • Organoids
  • Phosphoproteins / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Xenograft Model Antitumor Assays
  • YAP-Signaling Proteins / genetics
  • YAP-Signaling Proteins / metabolism*
  • YAP-Signaling Proteins / physiology


  • Adaptor Proteins, Signal Transducing
  • CALM2 protein, human
  • Calmodulin
  • DNA-Binding Proteins
  • Glucose Transporter Type 1
  • PRDM14 protein, human
  • Phosphoproteins
  • RNA-Binding Proteins
  • SLC2A1 protein, human
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human