Calpain restrains the stem cells compartment in breast cancer
| Autor: | Ramiro Mendoza-Maldonado, Marzia Raimondi, T Arnandis, M Bestagno, E Marcassa, Francesca Demarchi, Claudio Schneider, Francesca Cataldo |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Breast cancer mammospheres Cells Population Breast Neoplasms Symmetric division Stem cell marker Mice 03 medical and health sciences 0302 clinical medicine Cancer stem cell Report Animals Humans education Molecular Biology Cells Cultured Cell Proliferation education.field_of_study Cultured biology Calpain Cell growth Cell Biology USP1 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer cell Female MCF-7 Cells Neoplastic Stem Cells Developmental Biology biology.protein Cancer research Stem cell |
| Zdroj: | CELL CYCLE |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.1080/15384101.2015.1121325 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|