Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells.
Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells.
复制标题
DOI：
10.3390/ijms21176084
复制
发表时间：
2020-08-24
影响因子：
5.6
通讯作者：
Sikora E
中科院分区：
文献类型：
--
作者：
Bojko A;Staniak K;Czarnecka-Herok J;Sunderland P;Dudkowska M;Śliwińska MA;Salmina K;Sikora E
衰老/多倍化的诱导及其在癌症复发中的作用仍然是一个探索不足的问题。我们发现，MDA-MB-231和MCF-7乳腺癌细胞在阿霉素（dox）脉冲处理后发生可逆的衰老/多倍化。随后，衰老/多倍体细胞产生具有与亲本细胞相同量的DNA的后代（逃逸者）。在dox诱导的衰老/多倍化状态下，观察到自噬蛋白标记物如LC 3B II和p62/SQSTM 1的积累。然而，衰老细胞的特点是一个非常低的新的自噬体的形成和降解率，估计自噬指数。与衰老细胞相反，逃逸者具有显著增加的自噬指数和转录因子EB活化，但具有非降解货物的自噬抑制剂Rubicon和自噬囊泡的水平降低。这些结果有力地表明，逃逸者的自噬得到改善，特别是在MDA-MB-231细胞中。这两种细胞系的逃避者也容易受到dox诱导的衰老。然而，从衰老逃逸的MDA-MB-231细胞的特征在于γ H2 AX灶的数量较低，并且白细胞介素合成的模式与衰老细胞不同。因此，我们的研究表明，乳腺癌细胞可以经历从自噬状态解偶联的衰老，但自噬通量恢复可能是癌细胞逃避衰老/多倍性不可或缺的。
The induction of senescence/polyploidization and their role in cancer recurrence is still a poorly explored issue. We showed that MDA-MB-231 and MCF-7 breast cancer cells underwent reversible senescence/polyploidization upon pulse treatment with doxorubicin (dox). Subsequently, senescent/polyploid cells produced progeny (escapers) that possessed the same amount of DNA as parental cells. In a dox-induced senescence/polyploidization state, the accumulation of autophagy protein markers, such as LC3B II and p62/SQSTM1, was observed. However, the senescent cells were characterized by a very low rate of new autophagosome formation and degradation, estimated by autophagic index. In contrast to senescent cells, escapers had a substantially increased autophagic index and transcription factor EB activation, but a decreased level of an autophagy inhibitor, Rubicon, and autophagic vesicles with non-degraded cargo. These results strongly suggested that autophagy in escapers was improved, especially in MDA-MB-231 cells. The escapers of both cell lines were also susceptible to dox-induced senescence. However, MDA-MB-231 cells which escaped from senescence were characterized by a lower number of γH2AX foci and a different pattern of interleukin synthesis than senescent cells. Thus, our studies showed that breast cancer cells can undergo senescence uncoupled from autophagy status, but autophagic flux resumption may be indispensable in cancer cell escape from senescence/polyploidy.
登录
查看更多内容
影响因子：
3.9
作者：
Erenpreisa, Jekaterina;Salmina, Kristine;Anisimov, Alim P.
通讯作者：
Anisimov, Alim P.
DOI：
10.1124/jpet.112.197590
发表时间：
2012-12-01
影响因子：
3.5
作者：
Goehe, Rachel W.;Di, Xu;Gewirtz, David A.
通讯作者：
Gewirtz, David A.
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
4.6
作者：
Borczyk, Malgorzata;Sliwinska, Malgorzata Alicja;Radwanska, Kasia
通讯作者：
Radwanska, Kasia
影响因子：
6
作者：
Bojko, Agnieszka;Czarnecka-Herok, Joanna;Sikora, Ewa
通讯作者：
Sikora, Ewa