Search

Wnt signaling pathways are transmitted via 10 homologous frizzled receptors (FZD1-10) in humans. Reagents broadly inhibiting Wnt signaling pathways reduce growth and metastasis of many tumors, but their therapeutic development has been hampered by the side effect. Inhibitors targeting specific Wnt-FZD pair(s) enriched in cancer cells may reduce side effect, but the therapeutic effect of narrow-spectrum Wnt-FZD inhibitors remains to be established in vivo. Here, we developed a fragment of C. difficile toxin B (TcdBFBD), which recognizes and inhibits a subclass of FZDs, FZD1/2/7, and examined whether targeting this FZD subgroup may offer therapeutic benefits for treating breast cancer models in mice. Utilizing 2 basal-like and 1 luminal-like breast cancer models, we found that TcdBFBD reduces tumor-initiating cells and attenuates growth of basal-like mammary tumor organoids and xenografted tumors, without damaging Wnt-sensitive tissues such as bones in vivo. Furthermore, FZD1/2/7-positive cells are enriched in chemotherapy-resistant cells in both basal-like and luminal mammary tumors treated with cisplatin, and TcdBFBD synergizes strongly with cisplatin in inhibiting both tumor types. These data demonstrate the therapeutic value of narrow-spectrum Wnt signaling inhibitor in treating breast cancers.

Previous studies have found a processing difference between unaccusative sentences and unergative sentences. Theyargued that the difference is derived from a syntactic difference, i.e. an unaccusative sentence involves movement whereas anunergative sentence does not. In this study, we are going to show that those studies are uninterpretable due to uncontrolledstimuli and confounds in the materials. After examining their data anlysis, we argue that the effects they found does seem to bestable. This reopens the question whether there is a syntactic difference between unaccusative and unergative verbs.

The Unaccusative Hypothesis (UH) predicts that the subject of an unaccusative is mentally reactivated in the objectposition. Previous psycholinguistic studies have reported evidence of reactivation (Friedmann et al 2008, Koring et al 2012).However, these studies did not equate the unaccusative and unergative stimuli, resulting in confounds which jeopardize theirconclusions. We reexamined UH with two Visual World Paradigm experiments carefully controlled for the potential confoundsin the previous studies. On each trial, participants (n=40; n=52) saw 4 black-and-white drawings and heard a sentence. In thetest condition, but not the control condition, one image was semantically related to subject of the sentence. We measured theproportion of looks to the target image at three time regions after the verb onset and found a robust match-effect (p’s