Nicotine promotes apoptosis resistance of breast cancer cells and enrichment of side population cells with cancer stem cell-like properties via a signaling cascade involving galectin-3, α9 nicotinic acetylcholine receptor and STAT3.
Nicotine promotes apoptosis resistance of breast cancer cells and enrichment of side population cells with cancer stem cell-like properties via a signaling cascade involving galectin-3, α9 nicotinic acetylcholine receptor and STAT3.
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DOI：
10.1007/s10549-014-2912-z
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发表时间：
2014-05
影响因子：
3.8
通讯作者：
Ahmed, Hafiz
中科院分区：
文献类型：
--
作者：
Guha, Prasun;Bandyopadhyaya, Gargi;Polumuri, Swamy K.;Chumsri, Saranya;Gade, Padmaja;Kalvakolanu, Dhananjaya V.;Ahmed, Hafiz
尼古丁是烟草烟雾中的主要成瘾化合物，与肺癌、头颈癌、胰腺癌和乳腺癌的促进和进展有关，但癌症进展的详细机制仍然难以捉摸。在这里，我们发现尼古丁诱导乳腺癌细胞系和乳腺癌患者原发性肿瘤中半乳糖凝集素-3（一种抗凋亡β-半乳糖苷结合凝集素）的表达。尼古丁诱导的半乳糖凝集素-3上调是由于烟碱乙酰胆碱受体α9亚型（α 9 nAChR）的表达增加，其激活转录因子STAT 3，进而物理结合半乳糖凝集素-3（LGALS 3）启动子并诱导半乳糖凝集素-3转录。细胞内半乳糖凝集素-3增加乳腺癌细胞线粒体完整性并抑制化疗诱导的细胞凋亡。此外，尼古丁诱导的具有癌干细胞样特性的侧群细胞的富集受半乳糖凝集素-3表达的调节，并且可以通过瞬时敲低LGALS 3及其上游信号分子STAT 3和α 9 nAChR而显著降低。因此，半乳糖凝集素-3或其上游信号分子STAT 3或α 9 nAChR可能是预防尼古丁诱导的乳腺癌化疗耐药的潜在靶点。
Nicotine, a main addictive compound in tobacco smoke, has been linked to promotion and progression of lung, head and neck, pancreatic, and breast cancers, but the detailed mechanisms of cancer progression remain elusive. Here we show that nicotine induces the expression of galectin-3 (an anti-apoptotic β-galactoside-binding lectin) in breast cancer cell line and in primary tumors from breast cancer patients. Nicotine-induced up regulation of galectin-3 is due to an increased expression of α9 isoform of nicotinic acetylcholine receptor (α9nAChR), which activates transcription factor STAT3 that in turn, physically binds to galectin-3 (LGALS3) promoter and induces transcription of galectin-3. Intracellular galectin-3 increased mitochondrial integrity and suppressed chemotherapeutic-induced apoptosis of breast cancer cell. Moreover, nicotine induced enrichment of side population cells with cancer stem cell-like properties was modulated by galectin-3 expression and could be significantly reduced by transient knock down of LGALS3 and its upstream signaling molecules STAT3 and α9nAChR. Thus, galectin-3 or its upstream signaling molecule STAT3 or α9nAChR could be a potential target to prevent nicotine-induced chemoresistance in breast cancer.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
6.4
作者：
Dasgupta, Piyali;Rizwani, Wasia;Pillai, Smitha;Kinkade, Rebecca;Kovacs, Michelle;Rastogi, Shipra;Banerjee, Sarmistha;Carless, Melanie;Kim, Esther;Coppola, Domenico;Haura, Eric;Chellappan, Srikumar
通讯作者：
Chellappan, Srikumar
影响因子：
3.7
作者：
An Y;Kiang A;Lopez JP;Kuo SZ;Yu MA;Abhold EL;Chen JS;Wang-Rodriguez J;Ongkeko WM
通讯作者：
Ongkeko WM
DOI：
10.1073/pnas.1202653110
发表时间：
2013-03-26
影响因子：
11.1
作者：
Guha, Prasun;Kaptan, Engin;Ahmed, Hafiz
通讯作者：
Ahmed, Hafiz
影响因子：
4.8
作者：
Glinsky, Vladislav V.;Kiriakova, Galina;Glinsky, Gennadi V.
通讯作者：
Glinsky, Gennadi V.