Zhang Yue, Bi Jiajia, Zhu Hongtao, Shi Mei, Zeng Xianlu
a School of Life Science , Institute of Genetics and Cytology, Northeast Normal University , Changchun , China.
b Synthetic Biology Engineering Lab of Henan Province , School of Life Sciences and Technology, Xinxiang Medical University , Xinxiang , China.
Biosci Biotechnol Biochem. 2018 Oct;82(10):1733-1741. doi: 10.1080/09168451.2018.1484275. Epub 2018 Jun 18.
Triple negative breast cancer (TNBC) patients cannot benefit from EGFR-targeted therapy even though the EGFR is highly expressed, because patients exhibit resistance to these drugs. Unfortunately, the molecular mechanisms remain relatively unknown. ANXA2, highly expressed in invasive breast cancer cells, is closely related with poor prognosis, and acts as a molecular switch to EGFR activation. In this study, MDA-MB-231 cells and MCF7 cells were used. Our results showed that ANXA2 expression is inversely correlated with cell sensitivity to gefitinib. Knockdown of ANXA2 expression in MDA-MB-231 cells increased the gefitinib induced cell death. When ANXA2 was overexpressed in MCF7 cells, the gefitinib induced cell death was decreased. Furthermore, we demonstrated that phosphorylation of ANXA2 at Tyr23 is negatively correlated with the sensitivity of TNBC to gefitinib. Altogether, our results suggest a new role of ANXA2 in regulating sensitivity of TNBC MDA-MB-231 cells to the EGFR inhibitor gefitinib.
三阴性乳腺癌（TNBC）患者即使表皮生长因子受体（EGFR）高度表达也无法从EGFR靶向治疗中获益，因为患者对这些药物表现出耐药性。不幸的是，其分子机制仍相对不明。膜联蛋白A2（ANXA2）在侵袭性乳腺癌细胞中高度表达，与预后不良密切相关，并作为EGFR激活的分子开关。在本研究中，使用了MDA-MB-231细胞和MCF7细胞。我们的结果表明，ANXA2表达与细胞对吉非替尼的敏感性呈负相关。敲低MDA-MB-231细胞中的ANXA2表达可增加吉非替尼诱导的细胞死亡。当在MCF7细胞中过表达ANXA2时，吉非替尼诱导的细胞死亡减少。此外，我们证明了酪氨酸23位点的ANXA2磷酸化与TNBC对吉非替尼的敏感性呈负相关。总之，我们的结果表明ANXA2在调节TNBC MDA-MB-231细胞对EGFR抑制剂吉非替尼的敏感性方面具有新作用。
