Wnt/β-catenin 信號通路參與調節銅死亡

內容是2024年11月發表在《Cell Death Differ》上的與銅死亡調節通路有關的文獻。題目：Dysregulated Wnt/β-catenin signaling confers resistance to cuproptosis in cancer cells（Wnt/β-catenin信號失調使癌細胞對銅死亡產生抗性），PMID: 38987382。

單詞：

Dysregulated，失調的，修飾名詞，陳述具有“失調”特性的名詞

例句：Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts.

Confer，v.授予；商討；商議；協商；討論；交換意見；磋商；頒發；賦予；議定；商討；授與

confer on 授予；賦予

confer with商議；商量；商談

confer upon授予；賦予；給予

confer privilege授予的特權

摘要：

摘要部分可分為三個部分，第一個部分提出關鍵詞，研究熱點，以及本篇內容要解決的科學問題“癌細胞驅動銅死亡的分子機制”。第二部分解釋研究成果，作者發現Wnt/β-catenin/TCF4/ATP7B通路激活在CSC細胞中可產生銅死亡抗性，并進行驗證。第三部分概括研究結論，提出該研究意義。

Cuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy. However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. //銅死亡作為一種獨特的銅依賴的調節性細胞死亡方式，其特征在于三羧酸循環中脂酰化酶的堆積及隨后的鐵-硫蛋白簇的丟失。鑒于銅穩態失調可誘導銅死亡，探究其在腫瘤治療中作用吸引了極大的關注。然而，癌細胞逃避銅死亡的分子驅動尚未明確。

Here, we found that cuproptosis activates the Wnt/β-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/β-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/β-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the β-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis. //Knockdown of TCF4 or pharmacological Wnt/β-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. //第二部分，先出總結句，提出銅死亡激活研究通路。隨后對其機制進行解釋。進一步探究機制后進行驗證實驗。//這里，我們發現銅死亡激活Wnt/β-catenin通路。從機制上來說，銅可結合PDK1并促進其與AKT的結合，導致Wnt/β-catenin通路激活和腫瘤干細胞（CSC）的特性。尤其是，異常激活的Wnt/β-catenin信號通路使得CSC對銅死亡產生抵抗性。進一步的研究顯示β-catenin/TCF4轉錄復合物直接結合ATP7B啟動子，誘導其表達。ATP7B流出銅離子，減少細胞內銅并抑制銅死亡。敲除TCF4或藥理性阻斷Wnt/β-catenin可促進CSCs對硒銅誘導的銅死亡的敏感性。

These findings reveal a link between copper homeostasis regulated by the Wnt/β-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.// 這些結果解釋了Wnt/β-catenin通路調節的銅穩態和銅死亡敏感性之間的聯系，并通過選擇性誘導銅死亡為癌癥精確醫療戰略提出建議。

.單詞：

Lipoylated，脂酰化 lipoyl- 脂酰

Exploiting，vt. 剝削；開采；開拓；開發

Conferred，V-edv. 授予；（confer的過去式和過去分詞）

Intracellular, adj. 細胞內的；細胞內部的；發生在細胞內的；細胞內環境的；涉及細胞內成分的

Pharmacological, adj. 藥理學的

Precision, n. 精確性；準確性；精密度；精確度；精準；精密；精確化；精細；細致

adj.精確的；要求技術精確的

短語：

is characterized by……as sth，作為什么……其特點是

As sth can do sth, there is + n 或V-ing，表示因為…，所以…

However,過渡詞

Here,過渡詞

Mechanistically,從機制上看，介詞

a link between，什么之間的聯系

confers resistance to 賦予對…抗性

重要的動詞ing形式作為名詞，activation of，the sensitivity of sth to,

句子：

描述物品性質和特征，Sth is characterized by + n1 as +n2.

Here,we found that…總結

Mechanistically,主謂賓結構（作主語），V-ing （謂語）resulting in +結果

類似語句有，Further studies showed sth do sth，inducing its expression.

ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis.

過長的主謂賓，不作為主語接 V-ing形式。例如：These findings reveal a link between copper homeostasis regulated by the Wnt/β-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.

Notably,插入語，轉折過渡

摘要研究思路：

發現銅死亡激活Wnt/β-catenin通路，探討其上游機制。發現異常激活的Wnt/β-catenin通路可賦予癌細胞銅死亡抗性，探討其下游機制。進行驗證實驗。