title: Calpain restrains the stem cells compartment in breast cancer.
abstract: CAPNS1 is essential for the stability and function of ubiquitous CAPN1 and CAPN2. Calpain modulates by proteolytic cleavage many cellular substrates and its activity is often deregulated in cancer cells, therefore calpain inhibition has been proposed as a therapeutical strategy for a number of malignancies. Here we show that CAPNS1 depletion is coupled to impairment of MCF7 and MCF10AT cell lines growth on plate and defective architecture of mammary acini derived from MCF10A cells. In soft agar CAPNS1 depletion leads to cell growth increase in MCF7, and decrease in MCF10AT cells. In both MCF7 and MCF10AT, CAPNS1 depletion leads to the enlargement of the stem cell compartment, as demonstrated by mammosphere formation assays and evaluation of stem cell markers by means of FACS and western blot analysis. Accordingly, activation of calpain by thapsigargin treatment leads to a decrease in the stem cell reservoir. The expansion of the cancer stem cell population in CAPNS1 depleted cells is coupled to a defective shift from symmetric to asymmetric division during mammosphere growth coupled to a decrease in NUMB protein level.
authors.affiliation: a L.N.C.I.B., Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie AREA Science Park - Padriciano 99 , Trieste , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Raimondi
authors.affiliation: a L.N.C.I.B., Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie AREA Science Park - Padriciano 99 , Trieste , Italy.
authors.forename: E
authors.initials: E
authors.lastname: Marcassa
authors.affiliation: a L.N.C.I.B., Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie AREA Science Park - Padriciano 99 , Trieste , Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cataldo
authors.affiliation: a L.N.C.I.B., Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie AREA Science Park - Padriciano 99 , Trieste , Italy.
authors.forename: T
authors.initials: T
authors.lastname: Arnandis
authors.affiliation: a L.N.C.I.B., Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie AREA Science Park - Padriciano 99 , Trieste , Italy.
authors.forename: R
authors.initials: R
authors.lastname: Mendoza-Maldonado
authors.affiliation: c International Centre for Genetic Engineering and Biotechnology, AREA Science Park - Padriciano 99 , Trieste , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bestagno
authors.affiliation: a L.N.C.I.B., Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie AREA Science Park - Padriciano 99 , Trieste , Italy.|b Dipartimento di Scienze e Tecnologie Biomediche, Universita' degli Studi di Udine , Udine , Italy.
authors.forename: C
authors.initials: C
authors.lastname: Schneider
authors.affiliation: a L.N.C.I.B., Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie AREA Science Park - Padriciano 99 , Trieste , Italy.
authors.forename: F
authors.initials: F
authors.lastname: Demarchi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002154:Calpain / Q000172:deficiency*; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D002154:Calpain; C527669:CAPNS1 protein, human
keywords: Breast cancer Mammospheres; Calpain; Symmetric division; USP1