The Opportunity of Precision Medicine for Breast Cancer With Context‐Sensitive Tumor Suppressor Maspin

Abstract

To improve the precision of molecular diagnosis and to develop and guide targeted therapies of breast cancer, it is essential to determine mechanisms that underlie the specific tumor phenotypes. To this end, the application of a snapshot of gene expression profile for breast cancer diagnosis and prognosis is fundamentally challenged since the tissue-based data are derived from heterogonous cell types and are not likely to reflect the dynamics of context-dependent tumor progression and drug sensitivity. The intricate network of epithelial differentiation program can be concertedly controlled by tumor suppressor maspin, a homologue of clade B serine protease inhibitors (serpin), through its multifaceted molecular interactions in multiple subcellular localizations. Unlike most other serpins that are expressed in multiple and cell types, maspin is epithelial specific and has distinct roles in luminal and myoepithelial cells. Endogenously expressed maspin has been found in the nucleus and cytoplasm, and detected on the surface of cell membrane. It is also secreted free and as an exosomal cargo protein. Research in the field has led to the identification of the maspin targets and maspin-associated molecules, as well as the structural determinants of its suppressive functions. The current review discusses the possibility for maspin to serve as a cell type-specific and context-sensitive marker to improve the precision of breast cancer diagnosis and prognosis. These advancements further suggest a new window of opportunity for designing novel maspin-based chemotherapeutic agents with improved anti-cancer potency.

Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer

“…RT-qPCR assays revealed that the expression of maspin affected the gene expressions of cyclin D1, p21, vimentin MMP2, and MMP9 in xenograft tumors, which suggested that maspin may modulate these genes to regulate tumor growth in vivo. A previous study indicated that maspin blocked MMP9 expression in prostate carcinoma cells [25]. The previously mentioned genes are also potential target genes of HDAC1 indicating that maspin may correlate with the HDAC1 activity.…”

Brown Spider (Loxosceles) Venom Toxins as Potential Biotools for the Development of Novel Therapeutics

“…A particular member of the serpin family, maspin, has been previously studied because of its inhibitory potential in breast and prostate cancer development [100]. Recently, the designing novel maspin-based chemotherapeutic agents with improved anti-cancer potency was suggested [101]. Katsukawa and co-workers [102] suggested that serpin 5 secreted by epithelial cells acts as a component of the extracellular surveillance system that facilitates the clearance of premalignant epithelial cells.…”

Microvesicle Proteomic Profiling of Uterine Liquid Biopsy for Ovarian Cancer Early Detection

“…SERPINB5 is an epithelial-cell-specific member of the SERPIN family that lacks serine protease inhibition activity. Not much is known about its cellular functions in cancer, yet it has been implicated as cancer susceptibility gene and a prognostic factor in several cancer types (33). It has been also attributed a role as an exosomal protein (34).…”