Cystic Fibrosis, CFTR, and Colorectal Cancer

Scott, Patricia M.; Anderson, Kyle; Singhania, Mekhla; Cormier, Robert T.

doi:10.3390/ijms21082891

Cited by 70 publications

(78 citation statements)

References 143 publications

(201 reference statements)

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“…Chloride ion channel function has also been associated with CRC development, the most notable being the cystic fibrosis transmembrane conductance regulator CFTR in which CFTR gene mutations are associated with causing cystic fibrosis (CF) ( 205 ). CFTR is a tumor suppressor and downregulated expression of CFTR is linked to CRC not only in CF patients but in the general population ( 206 ).…”

Section: Sexual Dimorphism Of Ion Channel Function In Crcmentioning

confidence: 99%

Sexual Dimorphism in Colon Cancer

et al. 2020

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A higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18–44 years) with CRC have a better survival outcome compared to men of the same age or compared to older women (over 50 years), indicating a global incidence of sexual dimorphism in CRC rates and survival. This suggests a protective role for the sex steroid hormone estrogen in CRC development. Key proliferative pathways in CRC tumorigenesis exhibit sexual dimorphism, which confer better survival in females through estrogen regulated genes and cell signaling. Estrogen regulates the activity of a class of Kv channels (KCNQ1:KCNE3), which control fundamental ion transport functions of the colon and epithelial mesenchymal transition through bi-directional interactions with the Wnt/β-catenin signalling pathway. Estrogen also modulates CRC proliferative responses in hypoxia via the novel membrane estrogen receptor GPER and HIF1A and VEGF signaling. Here we critically review recent clinical and molecular insights into sexual dimorphism of CRC biology modulated by the tumor microenvironment, estrogen, Wnt/β-catenin signalling, ion channels, and X-linked genes.

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Section: Sexual Dimorphism Of Ion Channel Function In Crcmentioning

confidence: 99%

Sexual Dimorphism in Colon Cancer

et al. 2020

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“…Our results suggest a connection between the altered ATP8B1 gene expression levels and the respective change in viability and rate of cell proliferation. This effect could be mediated through CFTR gene which is known to be involved in familial colorectal cancer syndrome [33]. Silencing of tumor suppressor gene (TSG) could generate cis-or trans-affects with local or global implications that may lead to the increased proliferation [34].…”

Section: Discussionmentioning

confidence: 99%

Modulation of ATP8B1 Gene expression in Colorectal Cancer Cells Suggest its Role as a Tumor Suppressor

Althenayyan¹,

AlGhamdi²,

AlMuhanna³

et al. 2020

Preprint

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Sporadic colorectal cancer (CRC) develops through distinct molecular events. Loss of 18q chromosome is a conspicuous event in the progression of adenoma to carcinoma. There is limited information regarding the molecular effectors of this event. Earlier, we had reported ATP8B1 as a novel gene associated with CRC. ATP8B1 belongs to the family of P-type ATPases (P4 ATPase) that primarily function to facilitate the translocation of phospholipids. In this study, we attempt to implicate ATP8B1 gene located on chromosome 18q as a tumor suppressor gene. We studied indigenous patient data and confirmed the reduced expression of ATP8B1 in tumor samples. CRC cell lines were engineered with reduced and enhanced levels of ATP8B1 which provided a tool to study its role on cancer progression. Forced reduction of ATP8B1 expression either by CRISPR/Cas9 or shRNA was associated with increased growth and proliferation of CRC cell line - HT29. In contrast, overexpression of ATP8B1 resulted in reduced growth and proliferation of SW480 cell line. We generated a network of genes that are downstream of ATP8B1. Further, we provide predicted effect of modulation of ATP8B1 levels on this network and possible effect on fatty acid metabolism related genes. These results provide evidence in support of ATP8B1 being a tumor suppressor that may affect fatty acid metabolism in CRC.

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“…Colon cancer is about 5–10 times more prevalent in CF patients, and also occurs 2–3 decades earlier compared to the general population [ 77 , 78 ]. Gut inflammation is thought to play a key role in this predisposition to cancer in CF patients [ 41 , 78 ].…”

Section: Impact Of Gut Dysbiosis On Cystic Fibrosis Manifestationsmentioning

confidence: 99%

Impact of Altered Gut Microbiota and Its Metabolites in Cystic Fibrosis

et al. 2021

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Cystic fibrosis (CF) is the most common lethal, multisystemic genetic disorder in Caucasians. Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) protein are responsible for impairment of epithelial anionic transport, leading to impaired fluid regulation and pH imbalance across multiple organs. Gastrointestinal (GI) manifestations in CF may begin in utero and continue throughout the life, resulting in a chronic state of an altered intestinal milieu. Inherent dysfunction of CFTR leads to dysbiosis of the gut. This state of dysbiosis is further perpetuated by acquired factors such as use of antibiotics for recurrent pulmonary exacerbations. Since the gastrointestinal microbiome and their metabolites play a vital role in nutrition, metabolic, inflammatory, and immune functions, the gut dysbiosis will in turn impact various manifestations of CF—both GI and extra-GI. This review focuses on the consequences of gut dysbiosis and its metabolic implications on CF disease and possible ways to restore homeostasis.

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Cystic Fibrosis, CFTR, and Colorectal Cancer

Cited by 70 publications

References 143 publications

Sexual Dimorphism in Colon Cancer

Sexual Dimorphism in Colon Cancer

Modulation of ATP8B1 Gene expression in Colorectal Cancer Cells Suggest its Role as a Tumor Suppressor

Impact of Altered Gut Microbiota and Its Metabolites in Cystic Fibrosis

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