AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer.
AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer.
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AHNAK 通过靶向三阴性乳腺癌的多种途径抑制肿瘤增殖和侵袭
DOI：
10.1186/s13046-017-0522-4
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发表时间：
2017-05-12
期刊：
影响因子：
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通讯作者：
Xie X
中科院分区：
文献类型：
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作者：
Chen B;Wang J;Dai D;Zhou Q;Guo X;Tian Z;Huang X;Yang L;Tang H;Xie X
AHNAK，也被称为desmoyokin，是一个巨大的蛋白质，分子大小约为700 kDa，并发挥不同的功能，在不同类型的cancer.ResultsIn本研究中，我们证明，AHNAK mRNA水平下调7 8人乳腺癌细胞系，尤其是在三阴性乳腺癌（TNBC）细胞系。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患者生存不良相关的独立预后因素。AHNAK在两种TNBC细胞系MDA-MB-231和BT549中的过表达抑制了TNBC细胞的体外增殖和集落形成，并抑制了体内TNBC异种移植物的生长和肺转移。AHNAK对TNBC的抑瘤作用与AKT/MAPK信号通路和Wnt/β-catenin信号通路有关。一致的结果时，观察AHNAK敲低BT 20和MDA-MB-435 cells. ConclusionsTogether，我们的研究结果表明，AHNAK作为一种肿瘤抑制剂，负调控TNBC细胞增殖，TNBC异种移植物的生长和转移，通过不同的信号通路。
BackgroundAHNAK, 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.ResultsIn 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.ConclusionsTaken 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.