Shijie Sheng, Ph.D.

Professor, Department of Pathology and of Oncology, Karmanos Cancer Institute, Wayne State University

Host: Dr. Cristina Espinosa-Diez

“Maspin (Serpin B5) at the Crossroad of Stem Cell Differentiation Commitment”

Abstract

Maspin (AKA Serpin B5), an epithelial-specific protein in somatic tissues, is differentially regulated in development and in cancer. Interestingly, it exhibits seemingly contradicting biological functions depending on its differential expression patterns. It may be expressed in the nucleus and the cytoplasm, (n+c)Maspin, in the nucleus exclusively, (n)Maspin, or transcriptionally down-regulated. These findings challenge the earlier hypothesis that maspin simply acts as a bona fide tumor suppressor. Our recent evidence suggests that the patterns of maspin expression may mark and control the dynamics of stem cells in the process from self-renewal, differentiation priming, to established differentiated state. Our current mechanistic hypothesis suggests that in the primed cancer stem cell (P-CSC) state, maspin contemporaneously controls the epigenetic pausing and the proteostatic stress tolerance by inhibiting histone deacetylase 1 (HDAC1) in both the nucleus and the cytoplasm. Further, P-CSCs may be particularly sensitive to drugs that may push cellular stress beyond the tolerable level and may be more effectively targeted by major histocompatibility class I (MHC I)-specific immunotherapies.