The cystic fibrosis ΔF508 gene mutation and cancer

Padua, Rose Ann; Warren, N.; Grimshaw, David; Smith, M. T.; Whittaker, J. A.; Laidler, P.; Wright, P. R. S.; Douglas-Jones, Anthony; Fenaux, Pierre; Sharma, Anup; Horgan, Kieran; West, Robert R.

doi:10.1002/(sici)1098-1004(1997)10:1<45::aid-humu6>3.0.co;2-l

Cited by 32 publications

(8 citation statements)

References 17 publications

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“…Incidence of cancer among CF carriers is not consensual. Although some studies found that CF carriers appeared to be protected from melanoma [153,154], lung cancer [155] and prostate cancer [156], CF carriers were also reported to be associated with a modest increase in risk of pancreatic cancer, particularly those with earlier onset [157,158]. Another study reported no differences in incidence of breast cancer among F508del-CFTR carriers vs. the general population, but CF carriers presented more aggressive tumour phenotypes than non-carriers [159].…”

Section: Cf Carrier Status and Cancer Riskmentioning

confidence: 98%

What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?

Amaral

Pankonien

2020

IJMS

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One of the key features associated with the substantial increase in life expectancy for individuals with CF is an elevated predisposition to cancer, firmly established by recent studies involving large cohorts. With the recent advances in cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies and the increased long-term survival rate of individuals with cystic fibrosis (CF), this is a novel challenge emerging at the forefront of this disease. However, the mechanisms linking dysfunctional CFTR to carcinogenesis have yet to be unravelled. Clues to this challenging open question emerge from key findings in an increasing number of studies showing that CFTR plays a role in fundamental cellular processes such as foetal development, epithelial differentiation/polarization, and regeneration, as well as in epithelial–mesenchymal transition (EMT). Here, we provide state-of-the-art descriptions on the moonlight roles of CFTR in these processes, highlighting how they can contribute to novel therapeutic strategies. However, such roles are still largely unknown, so we need rapid progress in the elucidation of the underlying mechanisms to find the answers and thus tailor the most appropriate therapeutic approaches.

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Section: Cf Carrier Status and Cancer Riskmentioning

confidence: 98%

What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?

Amaral

Pankonien

2020

IJMS

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“…It is not clear at this point, however, whether the correlation between SLC26A3 and colon cancer is due to its role in HCO − 3 transport (and hence to regulation of pH i and local pH e ), a role in cellular Cl − homeostasis, or other less understood functions. Interestingly, mutations in the Cl − channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR), which is expressed in the luminal membrane of colonic crypt cells (Crawford et al, 1991), have also been suggested to be inversely associated with colon cancer (Padua et al, 1997), supporting the possibility for Cl − -dependent effects of SLC26A3. SLC26A3 has, furthermore, been proposed to modify cellular growth: heterologous expression of SLC26A3 induces growth suppression in various cancer cell lines (Chapman et al, 2002) while SLC26A3 knockout mice display altered morphology of the colonic mucosa with an expanded proliferative zone (Schweinfest et al, 2006).…”

Section: Function and Expression Of Hco−3 Transporters In Cancermentioning

confidence: 99%

Regulation and roles of bicarbonate transporters in cancer

et al. 2014

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A unifying feature of solid tumors is a markedly altered pH profile compared to normal tissues. This reflects that solid tumors, despite completely different origins, often share several phenotypic properties with implications for intra- and extracellular pH. These include: a metabolic shift in most cancer cells toward more acid-producing pathways, reflecting both oncogenic signaling and the development of hypoxia in poorly perfused regions of the tumors; the poorly perfused and often highly dense tumor microenvironment, reducing the diffusive flux of acid equivalents compared to that in normal tissues; and the markedly altered regulation of the expression and activity of pH-regulatory transport proteins in cancer cells. While some of these properties of tumors have been well described in recent years, the great majority of the research in this clinically important area has focused on proton transport, in particular via the Na+/H+ exchanger 1 (SLC9A1, NHE1) and various H+ ATPases. We have, however, recently demonstrated that at least under some conditions, including in vitro models of HER2 positive breast cancer, and measurements obtained directly in freshly dissected human mammary carcinomas, bicarbonate transporters such as the electroneutral Na+, HCO−3 cotransporter (SLC4A7, NBCn1), are upregulated and play central roles in pH regulation. In this review, we summarize and discuss the current knowledge regarding the regulation and roles of bicarbonate transporters in cancer. Furthermore, we present new analyses of publicly available expression data demonstrating widely altered expression levels of SLC4- and SLC26 family transporters in breast-, lung-, and colon cancer patients, and we hypothesize that bicarbonate transporter dysregulation may have both diagnostic and therapeutic potential in cancer treatment.

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“…10 Accumulating evidence has demonstrated that genetic variations in the CFTR gene may increase or decrease risk in a variety of cancers, including lung cancer. [11][12][13] This suggests that CFTR may function as a tumour suppressor or tumour promoter, depending on the type of tumour. Recently, CFTR was shown to be involved in inflammatory and apoptotic signalling pathways and the induction of multiple pathological phenotypes.…”

Section: Summary At a Glancementioning

confidence: 99%