Extracellular matrix (ECM) mechanical cues have powerful effects on cell proliferation, differentiation and death. Here, starting from an unbiased metabolomics approach, we identify synthesis of neutral lipids as a general response to mechanical signals delivered by cell–matrix adhesions. Extracellular physical cues reverberate on the mechanical properties of the Golgi apparatus and regulate the Lipin-1 phosphatidate phosphatase. Conditions of reduced actomyosin contractility lead to inhibition of Lipin-1, accumulation of SCAP/SREBP to the Golgi apparatus and activation of SREBP transcription factors, in turn driving lipid synthesis and accumulation. This occurs independently of YAP/TAZ, mTOR and AMPK, and in parallel to feedback control by sterols. Regulation of SREBP can be observed in a stiffened diseased tissue, and contributes to the pro-survival activity of ROCK inhibitors in pluripotent stem cells. We thus identify a general mechanism centered on Lipin-1 and SREBP that links the physical cell microenvironment to a key metabolic pathway.
See “News and Views” – Golgi mechanics controls lipid metabolism (doi:10.1038/s41556-019-0289-2)
The general objective of Cell biology and Cancer course is to cover different topics in cell biology including cell division, migration and membrane trafficking at different levels: molecular, cellular and in the living organism. The course will also cover different model systems, including organoids, and different tools such as optogenetics, microfabrication and microfluidics.
Colorectal cancer is the 3rd most common cancer and the 4th leading cause of cancer-related death worldwide. Each year, are declared 1.4 millions new cases of CRC and up to 2.4 millions in 2035 (WHO, 2012). Although the current treatments demonstrate certain efficiency, recurrence still occurs in 50% patients. The still unknown underlying mechanisms that conduct to this recurrence need to be elucidated, which could allow the appropriate therapy hoping to eradicate the relapse and the resulting death.
The team has found in mice a new parameter potentially involved in colon tumour progression : the mechanical strains associated to tumour growth pressure. The latter were indeed found as an activator of tumorigenic pathways of hyperproliferation and of tumorigenesis in the healthy epithelial cells compressed by neighbouring growing tumours, in the predisposition genetic context for 85% of human colorectal cancer.
Commercialized pharmacological inhibitors of such mechanosensitive tumorigenic pathway were already successfully tested in the team to block mechanical induction of tumorigenesis stimulation. The project consists in establishing in mice a new optimized and patentable treatment of colorectal cancer, based on specific magnetic targeting and ultrasonic progressive release of the colon tumour mechanical induction inhibitor.