Stem cell self-renewal and differentiation are coordinated to maintain tissue homeostasis and prevent cancer. Mutations causing stem cell proliferation are traditionally the focus of cancer studies. However, the contribution of the differentiating stem cell progenies in tumorigenesis is poorly characterized.

Researchers report that loss of the SOX transcription factor, Sox21a, blocks the differentiation programme of enteroblast (EB), the intestinal stem cell progeny in the adult Drosophila midgut. This results in EB accumulation and formation of tumors.

Sox21a tumor initiation and growth involve stem cell proliferation induced by the unpaired 2 mitogen released from accumulating EBs generating a feed-forward loop.
EBs found in the tumors are heterogeneous and grow towards the intestinal lumen. Sox21a tumors modulate their environment by secreting matrix metalloproteinase and reactive oxygen species.

Enterocytes surrounding the tumors are eliminated through delamination allowing tumor progression, a process requiring JNK activation. Our data highlight the tumorigenic properties of transit differentiating cells.

http://www.nature.com/ncomms/2015/151222/ncomms10219/full/ncomms10219.html