Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis I

Tumors occasionally express oncogenes via aberrant activation of transposable elements (TE), but a role for this process in oncogenesis was seldom demonstrated. Here, we identify expression of the hominid-restricted retrogene POU5F1B through aberrant activation of an endogenous retroviral promoter as a strong negative prognostic marker in colorectal cancer (CRC). We further determine that POU5F1B is membrane-enriched and interacts with ERBB2 and associated effectors, and fosters the proliferation and metastatic potential of CRC cells through intracellular signaling events and release of trans-acting molecules involved in cell growth, angiogenesis and cell adhesion. As POU5F1B is apparently non-essential and only lowly expressed in normal tissues, and as POU5F1B-containing TE-driven transcripts are detected in other tumors besides CRC, these data provide interesting leads for the development of cancer therapies. RNA-sequencing analysis of POU5F1B- and GFP-overexpressing SW480 cells.