Chen Bo, Wang Jin, Dai Danian, Zhou Qingyu, Guo Xiaofang, Tian Zhi, Huang Xiaojia, Yang Lu, Tang Hailin, Xie Xiaoming
Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 East Dongfeng Road, Guangzhou, 510060, People's Republic of China.
College of Pharmacy, University of South Florida, 12901 Bruce B Downs Blvd, MD30, Tampa, FL, 33612-4749, USA.
J Exp Clin Cancer Res. 2017 May 12;36(1):65. doi: 10.1186/s13046-017-0522-4.
AHNAK, also known as desmoyokin, is a giant protein with the molecular size of approximately 700 kDa and exerts diverse functions in different types of cancer.
In the present study, we demonstrated that AHNAK mRNA levels were down-regulated in 7 out of 8 human breast cancer cell lines, especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in patients with TNBC, the expression of AHNAK gene was inversely correlated with the tumor status (P = 0.015), lymph node status (P < 0.001), lymph node (LN) infiltration (P < 0.001) and TNM stage (P < 0.001). Moreover, down-regulated AHNAK expression was considered an independent prognostic factor associated with the poor survival of patients with TNBC. Overexpression of AHNAK in two TNBC cell lines, MDA-MB-231 and BT549, suppressed the in vitro TNBC cell proliferation and colony formation, and inhibited the in vivo TNBC xenograft growth and lung metastasis. The tumor suppressing effect of AHNAK in TNBC was associated with the AKT/MAPK signaling pathway and Wnt/β-catenin pathway. Consistent results were observed when AHNAK was knockdown in BT20 and MDA-MB-435 cells.
Taken together, our results suggest that AHNAK acts as a tumor suppressor that negatively regulates TNBC cell proliferation, TNBC xenograft growth and metastasis via different signaling pathways.
AHNAK，也被称为桥粒芯蛋白，是一种分子大小约为700 kDa的巨大蛋白质，在不同类型的癌症中发挥多种功能。
在本研究中，我们证明在8种人乳腺癌细胞系中的7种中，尤其是在三阴性乳腺癌（TNBC）细胞系中，AHNAK mRNA水平下调。此外，在TNBC患者中，AHNAK基因的表达与肿瘤状态（P = 0.015）、淋巴结状态（P < 0.001）、淋巴结（LN）浸润（P < 0.001）和TNM分期（P < 0.001）呈负相关。此外，AHNAK表达下调被认为是与TNBC患者不良生存相关的独立预后因素。在两种TNBC细胞系MDA-MB-231和BT549中过表达AHNAK可抑制体外TNBC细胞增殖和集落形成，并抑制体内TNBC异种移植瘤生长和肺转移。AHNAK在TNBC中的肿瘤抑制作用与AKT/MAPK信号通路和Wnt/β-连环蛋白通路有关。当在BT20和MDA-MB-435细胞中敲低AHNAK时，观察到了一致的结果。
综上所述，我们的结果表明AHNAK作为一种肿瘤抑制因子，通过不同的信号通路负向调节TNBC细胞增殖、TNBC异种移植瘤生长和转移。
