Cell-Matrix Interactions in Cancer

The overall objective is to define previously unknown and opposing roles of tissue stiffening in cancer development.Tissue stiffening occurring in most cancers is sensed by cells through mechanotransduction.

Against current dogma, our preliminary results indicate a dual role for tissue stiffening in cancer: transiently protecting the organism at an early stage of cancer development, but then promoting cancer progression at later stages, in significant part through specific yet undefined effects on mRNA-translation.This raises fundamental questions to be answered using state-of-the-art methods and models established in my laboratory, enhanced by our stellar collaborators.

In vitro models of physiological stiffness define molecular mechanisms and translational landscapes; transgenic mouse models determine the in vivo function in cancer; and breast cancer patient specimen identify the relation of translational reprograming to the clinical status and outcome.This project will advance our fundamental understanding of cancer development and progression and provide possibilities to target stiffening by exploiting the new mechanistic knowledge to improve cancer diagnosis and treatment.The outcome will also spark new research directions in mechanotransduction, mRNA-translation control, and senescence, relevant to a variety of areas such as development, cancer, aging, fibrosis, cardiovascular disease, wound healing, inflammation, tissue regeneration and cell reprograming.