Bhattacharya Rahul, Blankenheim Zachary, Scott Patricia M, Cormier Robert T
Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812, USA.
J Pers Med. 2022 May 25;12(6):868. doi: 10.3390/jpm12060868.
Cystic Fibrosis (CF) is a disease caused by mutations in the gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown to promote carcinogenesis. An example is the enhanced risk for several types of cancer in patients with CF, especially cancers of the GI tract. CFTR also acts as a tumor suppressor in diverse sporadic epithelial cancers in many tissues, primarily due to the silencing of CFTR expression via multiple mechanisms, but especially due to epigenetic regulation. This review provides an update on the latest research linking CFTR-deficiency to GI cancers, in both CF patients and in sporadic GI cancers, with a particular focus on cancer of the intestinal tract. It will discuss changes in the tissue landscape linked to CFTR-deficiency that may promote cancer development such as breakdowns in physical barriers, microbial dysbiosis and inflammation. It will also discuss molecular pathways and mechanisms that act upstream to modulate CFTR expression, such as by epigenetic silencing, as well as molecular pathways that act downstream of CFTR-deficiency, such as the dysregulation of the Wnt/β-catenin and NF-κB signaling pathways. Finally, it will discuss the emerging CFTR modulator drugs that have shown promising results in improving CFTR function in CF patients. The potential impact of these modulator drugs on the treatment and prevention of GI cancers can provide a new example of personalized cancer medicine.
囊性纤维化（CF）是一种由基因突变引起的疾病，严重影响肺部以及肺外组织，包括胃肠道（GI）。已表明，由突变或其表达下调导致的CFTR功能障碍会促进癌症发生。例如，CF患者患几种类型癌症的风险增加，尤其是胃肠道癌症。CFTR在许多组织的多种散发性上皮癌中也起着肿瘤抑制作用，主要是由于通过多种机制使CFTR表达沉默，尤其是由于表观遗传调控。本综述提供了关于CFTR缺陷与CF患者以及散发性胃肠道癌症中的胃肠道癌症之间最新研究的最新情况，特别关注肠道癌症。它将讨论与CFTR缺陷相关的组织格局变化，这些变化可能促进癌症发展，如物理屏障破坏、微生物群落失调和炎症。它还将讨论在CFTR表达调控上游起作用的分子途径和机制，如通过表观遗传沉默，以及在CFTR缺陷下游起作用的分子途径，如Wnt/β-连环蛋白和NF-κB信号通路的失调。最后，它将讨论在改善CF患者CFTR功能方面已显示出有前景结果的新兴CFTR调节剂药物。这些调节剂药物对胃肠道癌症治疗和预防的潜在影响可为个性化癌症医学提供一个新范例。
