ZNF32 promotes the self-renewal of colorectal cancer cells by regulating the LEPR-STAT3 signaling pathway.
ZNF32 promotes the self-renewal of colorectal cancer cells by regulating the LEPR-STAT3 signaling pathway.
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DOI：
10.1038/s41419-022-04530-4
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发表时间：
2022-02-03
影响因子：
9
通讯作者：
Fu X
中科院分区：
文献类型：
--
作者：
Li J;Li X;Lan L;Sun L;Li X;Li Y;Tian Y;Zhang T;Zhou Y;Mo C;Fu X
肿瘤干细胞具有自我更新和致瘤能力，在肿瘤发生和抗肿瘤治疗中发挥重要作用。我们以前的研究发现，Krüppel样家族成员（KLF）和锌指蛋白32（ZNF 32）在肿瘤发生中起致癌作用。然而，ZNF 32在CSCs中的作用和机制尚不清楚。我们的研究表明，ZNF 32在结直肠CSCs中高表达，这促进了其自我更新能力和致瘤性。ZNF 32在结直肠癌（CRC）细胞中的过表达增加了它们的自我更新能力。此外，我们确定了瘦素受体（LEPR）作为ZNF 32的下游靶基因，并证实ZNF 32介导的CRC自我更新的调节是通过LEPR信号转导和转录激活因子3（STAT 3）途径实现的。此外，ZNF 32调节干细胞中的核心转录因子SOX 2的表达。最后，我们证明ZNF 32和LEPR在结直肠癌组织中呈正相关。ZNF 32的表达与大肠癌患者的预后呈负相关。因此，在临床上治疗靶向ZNF 32-LEPR-STAT 3通路是诱人的。
Due to the self-renewal characteristics and tumorigenic abilities of cancer stem cells (CSCs), CSCs have been demonstrated to play vital roles in carcinogenesis and antitumor therapy. Our previous report found that Krüppel-like family members (KLFs) and zinc finger protein 32 (ZNF32) play oncogenic roles in carcinogenesis. However, the roles and mechanism of ZNF32 in CSCs are still unknown. Our study demonstrated that ZNF32 was highly expressed in colorectal CSCs, which promoted their self-renewal capacity and tumorigenicity. Overexpression of ZNF32 in colorectal cancer (CRC) cells increased their self-renewal capacity. Furthermore, we identified the leptin receptor (LEPR) as the downstream target gene of ZNF32 and verified that the ZNF32-mediated regulation of CRC self-renewal is achieved via the LEPR- signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ZNF32 regulated the expression of SOX2, a core transcription factor in stem cells. Finally, we demonstrated that ZNF32 and LEPR were positively correlated in CRC tissues. ZNF32 expression was negatively correlated with the prognosis of CRC patients. Therefore, therapeutically targeting the ZNF32-LEPR-STAT3 pathway in the clinic is tempting.
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影响因子：
5.6
作者：
Prieto-Vila M;Takahashi RU;Usuba W;Kohama I;Ochiya T
通讯作者：
Ochiya T
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
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影响因子：
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作者：
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通讯作者：
De Maria, R.
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
16.6
作者：
Fang F;Xia N;Angulo B;Carey J;Cady Z;Durruthy-Durruthy J;Bennett T;Sebastiano V;Reijo Pera RA
通讯作者：
Reijo Pera RA