PDF(Pubmed)
Abstract：
UNASSIGNED: Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and rapidly progresses. The overall response rate of PDAC to current treatment methods is still unsatisfactory. Thus, identifying novel targets and clarifying the underlying mechanisms associated with PDAC progression may potentially offer additional treatment strategies. AHNAK2 is aberrantly expressed in a variety of tumors and exerts pro-tumorigenic effects. However, the biological role of AHNAK2 in PDAC remains poorly understood.
UNASSIGNED: The expression of AHNAK2 in PDAC and paired non-tumor tissues was detected by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). Lentivirus knockdown was performed to investigate the impact of AHNAK2 on the biological function of pancreatic cancer cells. The subcutaneous cell-derived xenograft (CDX) model and the KPC spontaneous mouse model with AHNAK2 silencing were used to observe the effects of AHNAK2 on tumor growth and prognosis. The expression of c-MET at protein level in response to HGF treatment was assessed using western blot.
UNASSIGNED: Our results demonstrated that AHNAK2 was highly expressed in PDAC clinical samples and associated with poor prognosis. Knockdown of AHNAK2 significantly inhibited the proliferation, migration, and invasion of pancreatic cancer cells. AHNAK2 knockdown or knockout resulted in tumor growth suppression and prolonged survival in mice with PDAC. In addition, AHNAK2 and c-MET expression levels showed a significant positive correlation at the post-transcriptional level. Mechanistically, AHNAK2 promoted tumor progression by preventing c-MET degradation and persistently activating the HGF/c-MET signaling pathway.
UNASSIGNED: Overall, our study revealed that AHNAK2 plays an important role in PDAC progression by modulating the c-MET signaling pathway, and targeting AHNAK2 may be an effective therapeutic strategy for PDAC.
UNASSIGNED: The expression of AHNAK2 in PDAC and paired non-tumor tissues was detected by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). Lentivirus knockdown was performed to investigate the impact of AHNAK2 on the biological function of pancreatic cancer cells. The subcutaneous cell-derived xenograft (CDX) model and the KPC spontaneous mouse model with AHNAK2 silencing were used to observe the effects of AHNAK2 on tumor growth and prognosis. The expression of c-MET at protein level in response to HGF treatment was assessed using western blot.
UNASSIGNED: Our results demonstrated that AHNAK2 was highly expressed in PDAC clinical samples and associated with poor prognosis. Knockdown of AHNAK2 significantly inhibited the proliferation, migration, and invasion of pancreatic cancer cells. AHNAK2 knockdown or knockout resulted in tumor growth suppression and prolonged survival in mice with PDAC. In addition, AHNAK2 and c-MET expression levels showed a significant positive correlation at the post-transcriptional level. Mechanistically, AHNAK2 promoted tumor progression by preventing c-MET degradation and persistently activating the HGF/c-MET signaling pathway.
UNASSIGNED: Overall, our study revealed that AHNAK2 plays an important role in PDAC progression by modulating the c-MET signaling pathway, and targeting AHNAK2 may be an effective therapeutic strategy for PDAC.
摘要：
■胰腺导管腺癌（PDAC）恶性程度极高，进展迅速。PDAC对当前治疗方法的总体响应率仍然不令人满意。因此，确定新的靶标并阐明与PDAC进展相关的潜在机制可能会提供额外的治疗策略.AHNAK2在多种肿瘤中异常表达并发挥促肿瘤发生作用。然而,AHNAK2在PDAC中的生物学作用尚不清楚。
■通过免疫组织化学（IHC）和定量实时聚合酶链反应（qRT-PCR）检测PDAC和配对的非肿瘤组织中AHNAK2的表达。进行慢病毒敲除以研究AHNAK2对胰腺癌细胞生物学功能的影响。采用皮下细胞来源的异种移植（CDX）模型和AHNAK2沉默的KPC自发小鼠模型，观察AHNAK2对肿瘤生长和预后的影响。使用蛋白质印迹评估响应于HGF处理的蛋白水平的c-MET的表达。
■我们的结果表明，AHNAK2在PDAC临床样本中高表达，并与不良预后相关。敲除能显著抑制AHNAK2的增殖,迁移,和胰腺癌细胞的侵袭。AHNAK2敲低或敲除导致具有PDAC的小鼠中的肿瘤生长抑制和延长的存活。此外,AHNAK2和c-MET表达水平在转录后水平显示出显著的正相关。机械上,AHNAK2通过阻止c-MET降解和持续激活HGF/c-MET信号通路促进肿瘤进展。
■总的来说，我们的研究表明，AHNAK2通过调节c-MET信号通路在PDAC进展中发挥重要作用，靶向AHNAK2可能是PDAC的有效治疗策略。
■通过免疫组织化学（IHC）和定量实时聚合酶链反应（qRT-PCR）检测PDAC和配对的非肿瘤组织中AHNAK2的表达。进行慢病毒敲除以研究AHNAK2对胰腺癌细胞生物学功能的影响。采用皮下细胞来源的异种移植（CDX）模型和AHNAK2沉默的KPC自发小鼠模型，观察AHNAK2对肿瘤生长和预后的影响。使用蛋白质印迹评估响应于HGF处理的蛋白水平的c-MET的表达。
■我们的结果表明，AHNAK2在PDAC临床样本中高表达，并与不良预后相关。敲除能显著抑制AHNAK2的增殖,迁移,和胰腺癌细胞的侵袭。AHNAK2敲低或敲除导致具有PDAC的小鼠中的肿瘤生长抑制和延长的存活。此外,AHNAK2和c-MET表达水平在转录后水平显示出显著的正相关。机械上,AHNAK2通过阻止c-MET降解和持续激活HGF/c-MET信号通路促进肿瘤进展。
■总的来说，我们的研究表明，AHNAK2通过调节c-MET信号通路在PDAC进展中发挥重要作用，靶向AHNAK2可能是PDAC的有效治疗策略。
