Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25741600
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Cell+Death+Dis
2015 ; 6
(3
): e1675
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
How cell death shapes cancer
#MMPMID25741600
Labi V
; Erlacher M
Cell Death Dis
2015[Mar]; 6
(3
): e1675
PMID25741600
show ga
Apoptosis has been established as a mechanism of anti-cancer defense. Members of
the BCL-2 family are critical mediators of apoptotic cell death in health and
disease, often found to be deregulated in cancer and believed to lead to the
survival of malignant clones. However, over the years, a number of studies
pointed out that a model in which cell death resistance unambiguously acts as a
barrier against malignant disease might be too simple. This is based on
paradoxical observations made in tumor patients as well as mouse models
indicating that apoptosis can indeed drive tumor formation, at least under
certain circumstances. One possible explanation for this phenomenon is that
apoptosis can promote proliferation critically needed to compensate for cell
loss, for example, upon therapy, and to restore tissue homeostasis. However,
this, at the same time, can promote tumor development by allowing expansion of
selected clones. Usually, tissue resident stem/progenitor cells are a major
source for repopulation, some of them potentially carrying (age-, injury- or
therapy-induced) genetic aberrations deleterious for the host. Thereby, apoptosis
might drive genomic instability by facilitating the emergence of pathologic
clones during phases of proliferation and subsequent replication
stress-associated DNA damage. Tumorigenesis initiated by repeated cell attrition
and repopulation, as confirmed in different genetic models, has parallels in
human cancers, exemplified in therapy-induced secondary malignancies and
myelodysplastic syndromes in patients with congenital bone marrow failure
syndromes. Here, we aim to review evidence in support of the oncogenic role of
stress-induced apoptosis.
free
free
free
