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Morphogenesis, mechanics, and malignancy: How complex tissue architectures arise in cancers
Tissues are precisely built in their three-dimensional shape and the arrangement of specific cell types. This architecture breaks down as cancer-causing mutations transform normal tissue into tumor. How these architectural changes occur – through biophysical forces and gene regulatory networks that must coordinate across length and time scales – is a fundamental question in developmental and cancer biology. In this talk, I will discuss recently discovered mechanisms of mammalian tumor morphogenesis. Using a combination of computational modeling, genetic manipulations and biophysical measurements in vivo, I will describe how the biophysical drivers of tumor morphogenesis are distinct between simple monolayer and multilayered epithelia, and how initial architecture of the tissue-of-origin influences tumor morphogenesis. Our findings suggest that mechanical forces surrounding the proliferative cells within the tumor, so-called ‘cancer stem cells’, shape architecture of premalignant tumors and ultimately influence their progression into malignant cancer.
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