Intracellular NAD+ depletion induces autophagic death in multiple myeloma cells

被引：45

作者：

Cea, Michele ^{[1
,2
,3
]}

Cagnetta, Antonia ^{[1
,2
,3
]}

Patrone, Franco ^{[3
]}

Nencioni, Alessio ^{[3
]}

Gobbi, Marco ^{[3
]}

Anderson, Kenneth C. ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA

[3] IRCCS Univ Hosp San Martino IST, Dept Hematol & Oncol, Genoa, Italy

来源：

AUTOPHAGY | 2013年 / 9卷 / 03期

关键词：

multiple myeloma; nicotinamide phosphoribosyltransferase; PI3K/MTORC1; TFEB; cancer treatment;

D O I：

10.4161/auto.22866

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the proliferation of plasma cells in the bone marrow. Despite recent therapeutic advances, MM remains an incurable disease. Therefore, research has focused on defining new aspects in MM biology that can be therapeutically targeted. Compelling evidence suggests that malignant cells have a higher nicotinamide adenine dinucleotide (NAD+) turnover rate than normal cells, suggesting that this biosynthetic pathway represents an attractive target for cancer treatment. We recently reported that an intracellular NAD+-depleting agent, FK866, exerts its anti-MM effect by triggering autophagic cell death via transcriptional-dependent (transcription factor EB, TFEB) and -independent (PI3K-MTORC1) mechanisms. Our findings link intracellular NAD+ levels to autophagy in MM cells, providing the rationale for novel targeted therapies in MM.

引用

页码：410 / 412

页数：3