SPIB promotes anoikis resistance via elevated autolysosomal process in lung cancer cells
SPIB promotes anoikis resistance via elevated autolysosomal process in lung cancer cells
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SPIB 通过提高肺癌细胞的自溶酶体过程促进失巢凋亡抵抗
DOI：
10.1111/febs.15272
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Zhenyi Ma
中科院分区：
文献类型：
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作者：
Hua Zhang;Guobin Wang;Ruimin Zhou;Xiaobo Li;Yanan Sun;Yanzhe Li;Wei Du;Xiaojie Yan;Jie Yang;Xinzhong Chang;Zhe Liu;Zhenyi Ma
脱落诱导的细胞死亡是一种特殊类型的程序性细胞死亡，发生于正确的细胞外基质连接的丢失。失巢细胞抵抗是肿瘤侵袭和转移行为的重要机制。另一方面，自噬涉及受损细胞器的降解和错误折叠的蛋白质和细胞内成分的回收。然而，这两种细胞反应在肺癌细胞中的交集还没有得到广泛的研究。在这里，我们发现在基质剥夺后，淋巴细胞系特异性ETS转录因子SPIB被激活，并直接增强某些肺癌细胞中SNAP47的转录。丧失依附诱导的自噬通过激活SPIB显著增加对失巢凋亡的抵抗力。与这一功能一致，SPIB被短发夹RNA耗尽后，在基质剥夺时取消了SNAP47的转录激活。因此，这些数据描绘了SPIB在自噬介导的肺癌细胞失巢凋亡抵抗中的重要作用。因此，这些发现表明在体内操纵SPIB调节的通路和评估失巢抗性的影响值得进一步研究。数据库的RNA测序和芯片测序数据分别位于基因表达总览数据库中，登录号分别为GSE106592和GSE125561。
Anoikis (detachment‐induced cell death) is a specific type of programmed cell death which occurs in response to the loss of the correct extracellular matrix connections. Anoikis resistance is an important mechanism in cancer invasiveness and metastatic behavior. Autophagy, on the other hand, involves the degradation of damaged organelles and the recycling of misfolded proteins and intracellular components. However, the intersection of these two cellular responses in lung cancer cells has not been extensively studied. Here, we identified that upon matrix deprivation, the lymphocyte lineage‐specific Ets transcription factor SPIB was activated and directly enhancedSNAP47transcription in certain lung cancer cells. Loss of attachment‐induced autophagy significantly increased anoikis resistance by SPIB activation. Consistent with this function,SPIBdepletion by short hairpin RNA abrogatedSNAP47transcriptional activation upon matrix deprivation. Therefore, these data delineate an important role of SPIB in autophagy‐mediated anoikis resistance in lung cancer cells. Accordingly, these findings suggest that manipulating SPIB‐regulated pathwaysin vivoand evaluating the impact of anoikis resistance warrant further investigation.DatabaseRNA sequencing and ChIP sequencing data are available in Gene Expression Omnibus database under the accession numbers GSE106592 and GSE125561, respectively.