Nagaraju Ganji Purnachandra, Basha Riyaz, Rajitha Balney, Alese Olatunji Boladale, Alam Afroz, Pattnaik Subasini, El-Rayes Bassel
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA; Department of Biotechnology, Berhampur University, Bhanjavihar, Odisha 760007, India.
Institute for Cancer Research, Pre-Clinical Services, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Cancer Lett. 2016 Apr 1;373(1):12-18. doi: 10.1016/j.canlet.2016.01.003. Epub 2016 Jan 15.
Aquaporins (AQPs) are small (~30 kDa monomers) integral membrane water transport proteins that allow water to flow through cell membranes in reaction to osmotic gradients in cells. In mammals, the family of AQPs has thirteen (AQP0-12) unique members that mediate critical biological functions. Since AQPs can impact cell proliferation, migration and angiogenesis, their role in various human cancers is well established. Recently, AQPs have been explored as potential diagnostic and therapeutic targets in gastrointestinal (GI) cancers. GI cancers encompass multiple sites including the colon, esophagus, stomach and pancreas. Research in the last three decades has revealed biological aspects and signaling pathways critical for the development of GI cancers. Since the majority of these cancers are very aggressive and rapidly metastasizes, identifying effective targets is crucial for treatment. Preclinical studies have utilized inhibitors of specific AQPs and knock down of AQP expression using siRNA. Although several studies have explored the role of AQPs in colorectal, esophageal, gastric, hepatocellular and pancreatic cancers, there is no comprehensive review compiling the available information on GI cancers as has been published for other malignancies such as ovarian cancer. Due to the similarities and association of various sites of GI cancers, it is helpful to consider these results collectively in order to better understand the role of specific AQPs in critical GI cancers. This review summarizes the current knowledge of the role of AQPs in GI malignancies with particular focus on diagnosis and therapeutic applications.
水通道蛋白（AQPs）是一种小分子量的（约30 kDa单体）整合膜水转运蛋白，可使水在细胞渗透压梯度的作用下穿过细胞膜。在哺乳动物中，水通道蛋白家族有13个（AQP0 - 12）独特成员，它们介导关键的生物学功能。由于水通道蛋白可影响细胞增殖、迁移和血管生成，其在各种人类癌症中的作用已得到充分证实。最近，水通道蛋白已被探索作为胃肠道（GI）癌症潜在的诊断和治疗靶点。胃肠道癌症包括多个部位，如结肠、食管、胃和胰腺。过去三十年的研究揭示了对胃肠道癌症发展至关重要的生物学方面和信号通路。由于这些癌症中的大多数具有很强的侵袭性且迅速转移，确定有效的靶点对于治疗至关重要。临床前研究使用了特定水通道蛋白的抑制剂，并通过小干扰RNA（siRNA）敲低水通道蛋白的表达。尽管有几项研究探讨了水通道蛋白在结直肠癌、食管癌、胃癌、肝细胞癌和胰腺癌中的作用，但目前还没有像针对卵巢癌等其他恶性肿瘤那样，对胃肠道癌症的现有信息进行全面综述。由于胃肠道癌症各个部位之间存在相似性和关联性，综合考虑这些结果有助于更好地理解特定水通道蛋白在关键胃肠道癌症中的作用。本综述总结了目前关于水通道蛋白在胃肠道恶性肿瘤中作用的知识，特别关注诊断和治疗应用。
