膜聯(lián)蛋白為一類與酸性膜磷脂反應(yīng)的鈣結(jié)合蛋白家族，其氨基端區(qū)不同、羧基端區(qū)高度同源，參與膜轉(zhuǎn)運(yùn)、膜表面依賴鈣調(diào)蛋白的活動(dòng)等。膜聯(lián)蛋白A3（ANXA3）為膜聯(lián)蛋白家族非常重要成員，既往研究證實(shí)ANXA3參與細(xì)胞增殖、分化與凋亡、細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)和胞吞胞吐等一系列重要生理過(guò)程，其異常表達(dá)可能與多種癌癥的侵襲、進(jìn)展或轉(zhuǎn)移密切相關(guān)，其高表達(dá)可能促進(jìn)乳腺癌、肺腺癌、膽囊癌等的侵襲或轉(zhuǎn)移，其低表達(dá)可能促進(jìn)乳頭狀甲狀腺癌、前列腺癌等的轉(zhuǎn)移；此外，ANXA3可能通過(guò)促進(jìn)結(jié)腸癌血管生成促使腫瘤細(xì)胞的轉(zhuǎn)移。抑制或促進(jìn)ANXA3表達(dá)可能為癌癥治療提供新的方向。
2018年1月26日，英國(guó)《自然》旗下《細(xì)胞死亡與疾病》在線發(fā)表中國(guó)科學(xué)技術(shù)大學(xué)生命科學(xué)學(xué)院、復(fù)旦大學(xué)腫瘤研究所、復(fù)旦大學(xué)生物醫(yī)學(xué)研究院、細(xì)胞信號(hào)網(wǎng)絡(luò)協(xié)同創(chuàng)新中心、復(fù)旦大學(xué)附屬腫瘤醫(yī)院、安徽醫(yī)科大學(xué)第一附屬醫(yī)院、安徽省立醫(yī)院、安徽醫(yī)科大學(xué)附屬省立醫(yī)院、中國(guó)科學(xué)技術(shù)大學(xué)附屬第一醫(yī)院、安徽省腦功能與腦疾病重點(diǎn)實(shí)驗(yàn)室的柳素玲團(tuán)隊(duì)研究報(bào)告，發(fā)現(xiàn)下調(diào)ANXA3可以抑制腫瘤轉(zhuǎn)移并減少乳腺癌耐藥。
該研究發(fā)現(xiàn)，乳腺癌組織的ANXA3表達(dá)水平顯著上調(diào)。減少ANXA3表達(dá)能夠抑制癌細(xì)胞侵犯和破壞周圍正常組織，卻促進(jìn)癌細(xì)胞分裂增殖，無(wú)論體外還是體內(nèi)。此外，減少ANXA3表達(dá)能夠上調(diào)IκBα而抑制NFκB通路，引起間質(zhì)-上皮轉(zhuǎn)化和乳腺癌干細(xì)胞異質(zhì)性改變。此外，該研究證實(shí)減少ANXA3表達(dá)能夠增加乳腺癌細(xì)胞對(duì)化療藥物多柔比星的攝取和敏感性。減少ANXA3表達(dá)聯(lián)合多柔比星可以同時(shí)抑制腫瘤生長(zhǎng)和體內(nèi)轉(zhuǎn)移。
因此，該研究描述了ANXA3對(duì)調(diào)控乳腺癌干細(xì)胞和乳腺癌生長(zhǎng)轉(zhuǎn)移的作用及其機(jī)制，表明減少ANXA3表達(dá)聯(lián)合化療可能成為治療乳腺癌的新方法。
Cell Death Dis. 2018 Jan 26;9(2):126.
Downregulation of annexin A3 inhibits tumor metastasis and decreases drug resistance in breast cancer.
Ruikai Du, Bingjie Liu, Lei Zhou, Dong Wang, Xueyan He, Xiaojun Xu, Lixing Zhang, Chaoshi Niu, Suling Liu.
University of Science & Technology of China, Hefei, Anhui, China; Key Laboratory of Breast Cancer in Shanghai, Cancer Institute; Institutes of Biomedical Sciences; Innovation Center for Cell Signaling Network; Fudan University Shanghai Cancer Center, Shanghai, China; The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China; Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China; AnHui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China.
Annexin A3 (ANXA3) is dysregulated and plays an important role in various cancers. However, the role of ANXA3 in breast cancer is still unclear. Here, we observed that the expression level of ANXA3 was significantly upregulated in breast cancer tissues. ANXA3 knockdown inhibited cell invasion but promoted cell proliferation in both in vitro and in vivo assays. Furthermore, we found that ANXA3 knockdown inhibited the NFκB pathway via upregulating IκBα, resulting in mesenchymal-epithelial transition (MET) and a heterogeneity change of breast cancer stem cells (BCSCs). In addition, we demonstrated that ANXA3 knockdown increased the sensitivity of breast cancer cells to doxorubicin by increasing the drug uptake. The combination of ANXA3 knockdown and doxorubicin treatment simultaneously inhibited tumor growth and metastasis in vivo. This study described the role and mechanisms of ANXA3 in regulating BCSCs and breast cancer growth and metastasis, indicating that downregulating ANXA3 together with chemotherapy might be a novel therapeutic strategy for treating breast cancer.
DOI: 10.1038/s41419-017-0143-z
版權(quán)與免責(zé)聲明：本網(wǎng)頁(yè)的內(nèi)容由收集互聯(lián)網(wǎng)上公開(kāi)發(fā)布的信息整理獲得。目的在于傳遞信息及分享，并不意味著贊同其觀點(diǎn)或證實(shí)其真實(shí)性，也不構(gòu)成其他建議。僅提供交流平臺(tái)，不為其版權(quán)負(fù)責(zé)。如涉及侵權(quán)，請(qǐng)聯(lián)系我們及時(shí)修改或刪除。郵箱：sales@allpeptide.com