Mutations linked to loss of cell cycle control can render cells responsive to local differentiation cues.

Cell behaviors such as survival, proliferation, and death are governed by a multitude of cues, both intrinsic and extrinsic. To test whether a wild-type environment could encourage the survival and/or differentiation of neuronal progenitor cells with impaired cell cycle progression, we transplanted cells from and mutant zebrafish embryos into wild-type embryos, creating chimeric zebrafish with mutant cells in the developing eye. We found that when cells from or mutants were transplanted into wild-type hosts, survival and/or differentiation was almost always compromised in a manner consistent with cell-autonomous cell death.

Response to Comment on "Tumor-initiating cells establish an IL-33-TGF-β niche signaling loop to promote cancer progression".

Kamphuis argue that macrophages accumulated in the proximity of tumor-initiating cells do not express the high-affinity immunoglobulin E receptor FcεRIα. Although we cannot exclude the possibility of nonspecific binding of anti-FcεRIα antibody (clone MAR-1), we provide evidence that macrophages in squamous cell carcinomas express FcεRIα and that IL-33 induces FcεRIα expression in bone marrow cell-derived macrophages.

Tumor-initiating cells establish an IL-33-TGF-β niche signaling loop to promote cancer progression.

Targeting the cross-talk between tumor-initiating cells (TICs) and the niche microenvironment is an attractive avenue for cancer therapy. We show here, using a mouse model of squamous cell carcinoma, that TICs play a crucial role in creating a niche microenvironment that is required for tumor progression and drug resistance. Antioxidant activity in TICs, mediated by the transcription factor NRF2, facilitates the release of a nuclear cytokine, interleukin-33 (IL-33).

ADAP1 promotes invasive squamous cell carcinoma progression and predicts patient survival.

Invasive squamous cell carcinoma (SCC) is aggressive cancer with a high risk of recurrence and metastasis, but the critical determinants of its progression remain elusive. Here, we identify ADAP1, a GTPase-activating protein (GAP) for ARF6 up-regulated in TGF-β-responding invasive tumor cells, as a strong predictor of poor survival in early-stage SCC patients. Using a mouse model of SCC, we show that ADAP1 overexpression promotes invasive tumor progression by facilitating cell migration and breakdown of the basement membrane.