Salomon, R. | bioRxiv Science

bioRxiv2019

Single-cell RNAseq uncovers involution mimicry as an aberrant development pathway during breast cancer metastasis

Both luminal and basal breast cancer subtypes originate in the mammary luminal progenitor cell compartment. Basal breast cancer is associated with younger age, early relapse, and high mortality rate. Here we used unbiased droplet-based single-cell RNAseq to elucidate the cellular basis of tumour progression during the specification of the basal breast cancer subtype from the luminal progenitor population. Basal-like cancer cells resembled the alveolar lineage that is specified upon pregnancy and showed molecular features indicative of an interaction with the tumour microenvironment (TME) including epithelial-to-mesenchymal transition (EMT), hypoxia, lactation and involution. Involution signatures in luminal breast cancer tumours with alveolar lineage features were associated with worse prognosis and features of basal breast cancer. Our high-resolution molecular characterisation of the tumour ecosystem also revealed a highly interactive cell-cell network reminiscent of an involution process. This involution mimicry involves malignant education of cancer-associated fibroblasts and myeloid cell recruitment to support tissue remodelling and sustained inflammation. Our study shows how luminal breast cancer acquires an aberrant post-lactation developmental program that involves both cancer cells and cells from the TME, to shift molecular subtype and promote tumour progression, with potential to explain the increased risk and poor prognosis of breast cancer associated to childbirth.

cancer biology↗

bioRxiv2018

Sensorimotor conflicts alter perceptual and action monitoring

Bodily self-consciousness is defined as a set of prereflective representations of integrated bodily signals giving rise to self-identification, self-location and first-person perspective. While bodily self-consciousness is known to modulate perception, little is known about its influence on higher-level cognitive processes. Here, we manipulated bodily self-consciousness by applying sensorimotor conflicts while participants performed a perceptual task followed by confidence judgments. Results showed that sensorimotor conflicts altered perceptual monitoring by decreasing metacognitive performance. In a second experiment, we replicated this finding and extended our results by showing that sensorimotor conflicts also altered action monitoring, as measured implicitly through intentional binding. In a third experiment, we showed that effects on perceptual monitoring were induced specifically by sensorimotor conflicts related to the trunk and not to the hand. Taken together, our results suggest that bodily self-consciousness may serve as a scaffold for perceptual and action monitoring.

neuroscience↗