ZNF32 contributes to the induction of multidrug resistance by regulating TGF-β receptor 2 signaling in lung adenocarcinoma.
ZNF32 contributes to the induction of multidrug resistance by regulating TGF-β receptor 2 signaling in lung adenocarcinoma.
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ZNF32 通过调节肺腺癌中 TGF-β 受体 2 信号传导有助于诱导多药耐药性
DOI：
10.1038/cddis.2016.328
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发表时间：
2016-10-20
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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多药耐药（MDR）是导致癌症高死亡率的最重要因素之一，并且仍然是一个主要问题。我们以前发现，锌指蛋白32（ZNF 32），一个重要的转录因子与癌症在智人，保护肿瘤细胞对细胞死亡诱导的氧化应激和其他刺激。因此，我们假设ZNF 32可能使癌细胞对抗肿瘤药物的耐受性，因为在癌组织和耐药肺腺癌（AC）细胞中发现了较高的ZNF 32表达。在这项研究中，我们发现，ZNF 32是上调的Sp1（特异性蛋白1）在响应药物治疗和ZNF 32促进耐药性和保护AC细胞对顺铂或吉非替尼治疗。ZNF 32在AC细胞中的过表达通过增强MEK/ERK活化而赋予对EGFR（表皮生长因子受体）抑制剂的抗性。此外，ZNF 32可直接与TGF-βR2（transforming growth factor-betareceptor 2）启动子结合，促进其表达，ZNF 32诱导的抗性是通过增强TGF-βR2表达和激活TGF-βR2/SMAD 2途径介导的。在小鼠模型和离体培养的患者样本中，高水平的ZNF 32表达与较差的总体生存率和顺铂耐药性密切相关。ZNF 32可能是一种潜在的耐药诱导剂，在常规化疗和新型靶向治疗中，ZNF 32可以增加耐药相关基因TGF-βR2的表达，从而促进耐药的诱导。因此，ZNF 32相关的靶向治疗是一种潜在的新的辅助治疗，可能有效地防止化疗过程中多药耐药（MDR）的发生，提高AC患者的生存率。
Multidrug resistance (MDR) is one of the most important contributors to the high mortality of cancer and remains a major concern. We previously found that zinc finger protein 32 (ZNF32), an important transcription factor associated with cancer in Homo sapiens, protects tumor cells against cell death induced by oxidative stress and other stimuli. We thus hypothesized that ZNF32 might enable the tolerance of cancer cells to anti-tumor drugs because higher ZNF32 expression has been found in cancer tissues and in drug-resistant lung adenocarcinoma (AC) cells. In this study, we found that ZNF32 is upregulated by Sp1 (specificity protein 1) in response to drug treatment and that ZNF32 promotes drug resistance and protects AC cells against cisplatin or gefitinib treatment. ZNF32 overexpression in AC cells conferred resistance to EGFR (epidermal growth factor receptor) inhibitors by enhancing MEK/ERK activation. Moreover, ZNF32 was found to directly bind to the TGF-βR2 (transforming growth factor-beta receptor 2) promoter to promote its expression, and ZNF32-induced resistance was mediated by enhancing TGF-βR2 expression and activating the TGF-βR2/SMAD2 pathway. In both a mouse model and ex vivo cultured patient samples, a high level of ZNF32 expression was closely associated with worse overall survival and cisplatin resistance. ZNF32 appears to be a potential inducer of drug resistance that could increase the expression of the drug resistance-associated gene TGF-βR2 and subsequently facilitate the induction of drug resistance during both conventional chemotherapy and novel target therapy. Thus, ZNF32-associated target therapy is a potential novel adjuvant therapy that might effectively prevent the occurrence of multidrug resistance (MDR) during chemotherapy and improve the survival of patients with AC.
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ZNF32 通过调节 C1QBP 转录来防止氧化应激诱导的细胞凋亡。
影响因子：
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作者：
Li K;Gao B;Li J;Chen H;Li Y;Wei Y;Gong D;Gao J;Zhang J;Tan W;Wen T;Zhang L;Huang L;Xiang R;Lin P;Wei Y
通讯作者：
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影响因子：
4.2
作者：
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通讯作者：
Zhang, Wang-Gang
影响因子：
51.1
作者：
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通讯作者：
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影响因子：
64.8
作者：
Boussemart, Lise;Malka-Mahieu, Helene;Vagner, Stephan
通讯作者：
Vagner, Stephan