Hedgehog signalling, tissue stem cells, and cancer development - Rune Toftgård

Inappropriate reactivation of developmental signalling pathways such as the Hedgehog (Hh) pathway is a common event during cancer development.

Illustration showing the interaction of SUFU with GLI. A GLI3 peptide (blue) containing the recognition motif SYGH binds in a channel between the N-terminal (beige) and C-terminal (green) domains of SUFU.

Rune Toftgård closed his laboratory for experimental research at the end of 2021.

He had started his laboratory at Karolinska Institutet in 1985 and served as the Director of the Center for Innovative Medicine at Karolinska Institutet from 2006 to 2017 and as the Coordinator of the Strategic Programme on Cancer at Karolinska Institutet from 2010 to 2016. He was also a member of the Nobel Assembly at Karolinska Institutet from 1998 to 2017. Currently, he is active as a scientific advisor and mentor.

Hedgehog Signalling and Tissue Stem Cells

Mutational inactivation or activation of core components of the Hh-pathway underlies cell autonomous activation in basal cell carcinoma of the skin (BCC) and in medulloblastoma. In other tumour types such as colorectal, pancreatic and breast cancer additional activation mechanisms are present.

A major focus of research has been to understand the details of Hh signalling at the genetic, molecular, and structural level with emphasis on the key intracellular SUFU and GLI components. Secondly, to understand how aberrant activation of this pathway can drive cancer development and to devise new methods aimed at pharmacological inhibition of the Hh signalling pathway at the level of the GLI transcriptional effectors.

To understand cancer biology and how to best eradicate tumour cells, it is of key importance to know the biology of normal tissues including the nature of tissue stem and progenitor cells, their interconversions, and their ability to serve as cancer cells of origin. With this aim, the presence and functional properties of tissue stem cells marked by expression of Lgr5 and Lgr6 in skin and mammary gland have been characterised.

Rune Toftgård

H2 Department of Biosciences and Nutrition