Merck
  • Home
  • Search Results
  • Loss of Sirtuin 1 Alters the Secretome of Breast Cancer Cells by Impairing Lysosomal Integrity.

Loss of Sirtuin 1 Alters the Secretome of Breast Cancer Cells by Impairing Lysosomal Integrity.

Developmental cell (2019-04-16)
Arash Latifkar, Lu Ling, Amrit Hingorani, Eric Johansen, Amdiel Clement, Xiaoyu Zhang, John Hartman, Claudia Fischbach, Hening Lin, Richard A Cerione, Marc A Antonyak
ABSTRACT

The NAD+-dependent deacetylase Sirtuin 1 (SIRT1) is down-regulated in triple-negative breast cancer. To determine the mechanistic basis by which reduced SIRT1 expression influences processes related to certain aggressive cancers, we examined the consequences of depleting breast cancer cells of SIRT1. We discovered that reducing SIRT1 levels decreased the expression of one particular subunit of the vacuolar-type H+ ATPase (V-ATPase), which is responsible for proper lysosomal acidification and protein degradation. This impairment in lysosomal function caused a reduction in the number of multi-vesicular bodies (MVBs) targeted for lysosomal degradation and resulted in larger MVBs prior to their fusing with the plasma membrane to release their contents. Collectively, these findings help explain how reduced SIRT1 expression, by disrupting lysosomal function and generating a secretome comprising exosomes with unique cargo and soluble hydrolases that degrade the extracellular matrix, can promote processes that increase breast-cancer-cell survival and invasion.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Leupeptin hydrochloride, microbial, ≥90% (HPLC)
Sigma-Aldrich
Anti-TAPA-1 (CD81) Antibody, clone 5A6, clone 5A6, from mouse
Sigma-Aldrich
L-Arginine-13C6,15N4 hydrochloride, 99 atom % 15N, 99 atom % 13C, 95% (CP)