ANO1: More Than Just Calcium-Activated Chloride Channel in Cancer

Guo, Shengli; Zhang, Linna; Li, Na

doi:10.3389/fonc.2022.922838

Cited by 14 publications

(13 citation statements)

References 91 publications

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“…Consistent with expectations from these results, our in vivo data underscore the role of ANO1 in increasing metastatic gene expression, cancer cell bone relocation, and osteoclastic bone lysis. Such a connection between ANO1 and bone metastasis has been demonstrated by previous studies exploring ANO1 as a regulator of lung metastatic potential of gastric cancer 40 . However, the mechanism behind the control of ANO1 expression in certain metastatic cancers has not been elucidated yet.…”

Section: Discussionsupporting

confidence: 55%

Promoter hypermethylation as a novel regulator of ANO1 expression and function in prostate cancer bone metastasis

Shin,

Kim,

2024

Sci Rep

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Despite growing evidence implicating the calcium-activated chloride channel anoctamin1 (ANO1) in cancer metastasis, its direct impact on the metastatic potential of prostate cancer and the possible significance of epigenetic alteration in this process are not fully understood. Here, we show that ANO1 is minimally expressed in LNCap and DU145 prostate cancer cell lines with low metastatic potential but overexpressed in high metastatic PC3 prostate cancer cell line. The treatment of LNCap and DU145 cells with DNMT inhibitor 5-aza-2′-deoxycytidine (5-Aza-CdR) potentiates ANO1 expression, suggesting that DNA methylation is one of the mechanisms controlling ANO1 expression. Consistent with this notion, hypermethylation was detected at the CpG island of ANO1 promoter region in LNCap and DU145 cells, and 5-Aza-CdR treatment resulted in a drastic demethylation at promoter CpG methylation sites. Upon 5-Aza-CdR treatment, metastatic indexes, such as cell motility, invasion, and metastasis-related gene expression, were significantly altered in LNCap and DU145 cells. These 5-Aza-CdR-induced metastatic hallmarks were, however, almost completely ablated by stable knockdown of ANO1. These in vitro discoveries were further supported by our in vivo observation that ANO1 expression in xenograft mouse models enhances the metastatic dissemination of prostate cancer cells into tibial bone and the development of osteolytic lesions. Collectively, our results help elucidate the critical role of ANO1 expression in prostate cancer bone metastases, which is epigenetically modulated by promoter CpG methylation.

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Section: Discussionsupporting

confidence: 55%

Promoter hypermethylation as a novel regulator of ANO1 expression and function in prostate cancer bone metastasis

Shin,

Kim,

2024

Sci Rep

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“…The largest range of copy number values was observed for ANO1, which ranged from the loss of both copies in the CCK81 cell line derived from a metastasis of colorectal cancer to an estimated 17 copies in the FADU hypopharyngeal carcinoma cell line [81]. A number of other cell lines from different tumor types also had high-level ANO1 amplifications (data not shown), consistent with frequent amplifications of ANO1 in head and neck squamous carcinoma (HNSCC), bladder, and breast cancers as part of the amplification of the chromosomal region 11q13 [104][105][106]. Several other imprinted genes also had high-level amplifications in individual cell lines.…”

Section: Distribution Of the Copy Number Values And Gene Region-avera...mentioning

confidence: 60%

“…The strongest association with drug response was observed for the methylation of exon 1 of ANO1, the gene encoding anoctamin 1 at 11q13.3. ANO1, a Ca 2+ -activated chloride channel protein, is involved in cancer cell proliferation, cell cycle changes, cell migration, and metastasis [104][105][106]. Methylation of the TSS200, the 5′ UTR, and the 1st exon of DLX5, which is located on 7q21.3 and encodes the distal-less homeobox 5 protein, was associated with sensitivity to XMD8-85 (− 0.3865 ≤ ρ ≤ − 0.3697, 2.74 × 10 -9 ≤ p 0 ≤ 1.46 × 10 -8 , 5.65 × 10 -7 ≤ p FDR ≤ 1.9 7 × 10 -6 ; Additional file 9: Table S6).…”

Section: Analysis Of Association Of Methylation Of Imprinted Genes In...mentioning

confidence: 99%

Increased copy number of imprinted genes in the chromosomal region 20q11-q13.32 is associated with resistance to antitumor agents in cancer cell lines

et al. 2022

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Background Parent of origin-specific allelic expression of imprinted genes is epigenetically controlled. In cancer, imprinted genes undergo both genomic and epigenomic alterations, including frequent copy number changes. We investigated whether copy number loss or gain of imprinted genes in cancer cell lines is associated with response to chemotherapy treatment. Results We analyzed 198 human imprinted genes including protein-coding genes and noncoding RNA genes using data from tumor cell lines from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer datasets. We examined whether copy number of the imprinted genes in 35 different genome locations was associated with response to cancer drug treatment. We also analyzed associations of pretreatment expression and DNA methylation of imprinted genes with drug response. Higher copy number of BLCAP, GNAS, NNAT, GNAS-AS1, HM13, MIR296, MIR298, and PSIMCT-1 in the chromosomal region 20q11-q13.32 was associated with resistance to multiple antitumor agents. Increased expression of BLCAP and HM13 was also associated with drug resistance, whereas higher methylation of gene regions of BLCAP, NNAT, SGK2, and GNAS was associated with drug sensitivity. While expression and methylation of imprinted genes in several other chromosomal regions was also associated with drug response and many imprinted genes in different chromosomal locations showed a considerable copy number variation, only imprinted genes at 20q11-q13.32 had a consistent association of their copy number with drug response. Copy number values among the imprinted genes in the 20q11-q13.32 region were strongly correlated. They were also correlated with the copy number of cancer-related non-imprinted genes MYBL2, AURKA, and ZNF217 in that chromosomal region. Expression of genes at 20q11-q13.32 was associated with ex vivo drug response in primary tumor samples from the Beat AML 1.0 acute myeloid leukemia patient cohort. Association of the increased copy number of the 20q11-q13.32 region with drug resistance may be complex and could involve multiple genes. Conclusions Copy number of imprinted and non-imprinted genes in the chromosomal region 20q11-q13.32 was associated with cancer drug resistance. The genes in this chromosomal region may have a modulating effect on tumor response to chemotherapy.

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“…Several ANO1 modulators have been reported since it was identified as a calcium-activated chloride channel in 2008 [ 46 ]. ANO1 inhibition has shown therapeutic potential as an anticancer, anti-asthmatic, and antinociceptive agent [ 16 , 46 ]. Potentiation of ANO1 can provide health benefits for human diseases such as salivary gland dysfunction, cystic fibrosis, dry eye syndrome, and intestinal hypomotility [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the ANO1 gene is located within the 11q13 amplicon which is frequently amplified in many malignant tumors and ANO1 has been reported to be highly expressed in a variety of human cancers including gastrointestinal stromal tumor, head and neck squamous cell carcinoma, prostate cancer, breast cancer, pancreatic cancer, and glioblastoma [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. In addition, the increased expression of ANO1 is known to be associated with poor prognosis in cancer patients [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of ANO1 by Cis- and Trans-Resveratrol and Their Anticancer Activity in Human Prostate Cancer PC-3 Cells

Jeon

Lee

et al. 2023

IJMS

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Anoctamin1 (ANO1), a calcium-activated chloride channel, is involved in the proliferation, migration, and invasion of various cancer cells including head and neck squamous cell carcinoma, lung cancer, and prostate cancer. Inhibition of ANO1 activity or downregulation of ANO1 expression in these cancer cells is known to exhibit anticancer effects. Resveratrol, a natural polyphenol abundant in wines, grapes, berries, soybeans, and peanuts, shows a wide variety of biological effects including anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated the effects of two stereoisomers of resveratrol on ANO1 activity and found that cis- and trans-resveratrol inhibited ANO1 activity with different potencies. Cis- and trans-resveratrol inhibited ANO1 channel activity with IC50 values of 10.6 and 102 μM, respectively, and had no significant effect on intracellular calcium signaling at 10 and 100 μM, respectively. In addition, cis-resveratrol downregulated mRNA and protein expression levels of ANO1 more potently than trans-resveratrol in PC-3 prostate cancer cells. Cis- and trans-resveratrol significantly reduced cell proliferation and cell migration in an ANO1-dependent manner, and both resveratrol isomers strongly increased caspase-3 activity, PARP cleavage, and apoptotic sub-G1 phase ratio in PC-3 cells. These results revealed that cis-resveratrol is a potent inhibitor of ANO1 and exhibits ANO1-dependent anticancer activity against human metastatic prostate cancer PC-3 cells.

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ANO1: More Than Just Calcium-Activated Chloride Channel in Cancer

Cited by 14 publications

References 91 publications

Promoter hypermethylation as a novel regulator of ANO1 expression and function in prostate cancer bone metastasis

Promoter hypermethylation as a novel regulator of ANO1 expression and function in prostate cancer bone metastasis

Increased copy number of imprinted genes in the chromosomal region 20q11-q13.32 is associated with resistance to antitumor agents in cancer cell lines

Inhibition of ANO1 by Cis- and Trans-Resveratrol and Their Anticancer Activity in Human Prostate Cancer PC-3 Cells

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