Abstract：
The hepatocyte nuclear factor-1 (HNF1ɑ) is a transcription factor that contributes to several kinds of cancer progression. However, very little is known regarding the mechanisms underlying the activity of HNF1ɑ. We aimed to explore the role of HNF1ɑ in the progress of colorectal cancer (CRC) and elucidate its molecular mechanism. HNF1ɑ expression was upregulated in CRC samples and high expression of HNF1ɑ was associated with poor prognosis of CRC patients. HNF1α knockdown and overexpression inhibited and promoted proliferation, migration and invasion of CRC cells both in vitro and in vivo respectively. Mechanistically, HNF1ɑ increased the transcriptional activity of hexokinase domain component 1（HKDC1）promoter, thus activated AKT/AMPK signaling. Meanwhile, HKDC1 upregulation was important for the proliferation, migration and invasion of CRC cells and knockdown of HKDC1 significantly reversed the proliferation, migration and invasion induced by HNF1α overexpression. Taken together, HNF1ɑ contributes to CRC progression and metastasis through binding to HKDC1 and activating AKT/AMPK signaling. Targeting HNF1ɑ could be a potential therapeutic strategy for CRC patients.
摘要：
肝细胞核因子-1(HNF1α)是多种肿瘤进展的转录因子。然而,关于HNF1α活性的机制知之甚少。本研究旨在探讨HNF1α在结直肠癌(CRC)进展中的作用及其分子机制。CRC标本中HNF1α表达上调，高表达与CRC患者预后不良相关。HNF1α敲低和过表达抑制和促进增殖，CRC细胞在体外和体内的迁移和侵袭。机械上,HNF1α增加己糖激酶结构域组分1（HKDC1）启动子的转录活性,从而激活AKT/AMPK信号。同时,HKDC1上调对增殖很重要，HKDC1基因敲除后可显著逆转CRC细胞的增殖、迁移和侵袭,HNF1α过表达诱导的迁移和侵袭。一起来看,HNF1α通过与HKDC1结合并激活AKT/AMPK信号参与CRC的进展和转移。靶向HNF1α可能是CRC患者的潜在治疗策略。
