Loss of primary cilia occurs early in breast cancer development

Menzl, Ina; LeBeau, Lauren; Pandey, Ritu; Hassounah, Nadia B.; Li, Frank W.; Nagle, Ray B.; Weihs, Karen L.; McDermott, Kimberly M.

doi:10.1186/2046-2530-3-7

Cited by 123 publications

(132 citation statements)

References 60 publications

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“…In addition, primary cilia may participate in the development and progression of cancer, such as breast cancer (33). At the molecular level, the function of dub in ciliogenesis is regulated by phosphorylation which in turn depends on Frizzled-2-mediated noncanonical Wntsignaling (34). Here our study suggested Wnt3a inhibited the formation of cilia in breast cancer cells.…”

Section: Discussionmentioning

confidence: 48%

Wnt Signaling Inhibits the Growth of Primary Cilia and Activates CyclinD1, Snail and VEGFA Expression in Breast Cancer Cell Line MDA-MB-231

Deng¹

2015

AJLS

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Abstract:Although Wnt/β-catenin signaling has been shown to be essential in the process of cancer formation, it is unclear how Wnt3a signaling pathway regulates abnormal proliferation and differentiation of breast cancer cells. Here, we found overexpression of Wnt3a stimulated the expression of the Wntsignaling's downstream genes such as LRP6, Naked, Axin1, DVL-2, β-catenin, and TCF-1 in breast cancer cell line MDA-MB-231.Primarycilia is deemed as sensory cell antennae thatcoordinates a large number of cellular signaling pathways, sometimes coupling cell division and differentiation. Primary cilia were found on the surface of this cell line. Overexpression of Wnt3a decreased the formation of primary cilia. Inhibition of Wnt3a with Calphostin C facilitated growth of primary cilia. Wnt3a activated cell proliferation gene of CyclinD1. In contrary, Calphostin C decreased the promotional effect on proliferation of MDA-MB-231. The Snail family of transcription factor has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development. Wnt3a promoted MDA-MB-231 induced expression of Snail, whose effect was inhibited by Calphostin-C. VEGFA activity was originally referred to as vascular permeability factor and had been shown to stimulate endothelial cell mitogenesis and cell migration and increased microvascular permeability. Wnt3a facilitated MDA-MB-231 induced expression of VEGFA, as well as Calphostin-C suppressed its effect. Taken together, these results suggested thatWnt3a signaling played an important role in regulating the formation of breast cancer.

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Section: Discussionmentioning

confidence: 48%

Wnt Signaling Inhibits the Growth of Primary Cilia and Activates CyclinD1, Snail and VEGFA Expression in Breast Cancer Cell Line MDA-MB-231

Deng¹

2015

AJLS

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“…However, primary cilia are absent or shortened in several types of cancer, including kidney, skin, brain, breast, pancreas, and prostate. [101][102][103][104][105][106][107][108][109][110] It is also reported that a reduction in cilia frequency relative to adjacent normal tissues was observed in renal cell carcinoma (clear cell), breast cancers, melanoma, basal cell carcinoma, medulloblastoma, and pancreatic cancer. 104,105,107,[110][111][112][113][114][115][116][117][118][119] Genetic studies further support that the loss of cilia can increase tumor incidence in basal cell carcinoma and medulloblastoma.…”

Section: Primary Cilia and Tumorigenesismentioning

confidence: 94%

“…[101][102][103][104][105][106][107][108][109][110] It is also reported that a reduction in cilia frequency relative to adjacent normal tissues was observed in renal cell carcinoma (clear cell), breast cancers, melanoma, basal cell carcinoma, medulloblastoma, and pancreatic cancer. 104,105,107,[110][111][112][113][114][115][116][117][118][119] Genetic studies further support that the loss of cilia can increase tumor incidence in basal cell carcinoma and medulloblastoma. [102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117] It has been reported that primary cilia are lost early in breast cancer development on both the cancer cells and their surrounding stromal cells.…”

Section: Primary Cilia and Tumorigenesismentioning

confidence: 94%

“…However, loss of cilia may not be sufficient to initiate tumorigenesis in the mammary gland. 110 Furthermore, the loss of primary cilia is not associated with positive staining of Ki67 (a cell proliferation marker) in melanoma, renal cell carcinoma, and pancreatic cancer. 104,105,112 Therefore, loss of cilia may not be due to a result of altered cellular proliferation rates; primary cilia dysfunction in cancers may be caused by other mechanisms, such as a loss of genes required for ciliogenesis, potentially resulting from mutagenesis or genomic instability.…”

Section: Primary Cilia and Tumorigenesismentioning

confidence: 99%

“…112 Abnormal Hh activity is also involved in various cancers, including basal cell carcinomas, medulloblastomas, rhabdomyosarcomas, glioblastomas, and breast and prostate cancers. [108][109][110] WNT molecules and their downstream effectors regulate various stages of cancer development including initiation, progression, and metastasis. Furthermore, expression of PDGF and its receptor was found in various tumors including those in the CNS, germ cells, and the gastrointestinal system.…”

Section: Primary Cilia and Tumorigenesismentioning

confidence: 99%

See 2 more Smart Citations

Primary Cilium-Mediated Crosstalk of Signaling Cascades in Ciliogenesis: Implications for Tumorigenesis and Senescence

Suizu¹,

Hirata²,

Ishigaki³

et al. 2016

Cell Communication Insights

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Primary cilium, a small, antenna-like, microtubule (MT)-based extracellular organelle, which extends from the surface of all types of human cells, has important roles in various cellular functions, including planar cell polarity, cell growth, cell cycle, cell migration, transactivation, and immune response. Primary cilium-mediated signaling cascades are initiated by chemosensing environmental signals, such as growth factors and morphogens that activate ciliary receptor-mediated signal transduction, or by mechanosensing of fluid flow followed by induction of intracellular Ca 2+ flux. Owing to the versatile tools that cilia have, enabling various cellular functions, ciliary dysfunction causes several cilium-related human disorders such as ciliopathies. Here, we focus on the structure and biogenesis of primary cilium and discuss primary cilium-mediated crosstalk of the molecular mechanisms of signaling cascades in ciliogenesis, tumorigenesis, and senescence.

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Genetic variants in primary cilia‐related genes associated with the prognosis of first‐line chemotherapy in colorectal cancer

Qiu,

Chen,

Ben

et al. 2024

Cancer Medicine

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BackgroundPrimary cilia are antenna‐like organelles that conduct physical and chemical signals, which affect cell proliferation, migration, and differentiation. Some researchers have reported the correlation between primary cilia‐related genes and prognosis of colorectal cancer (CRC).MethodsThe association between single nucleotide polymorphisms (SNPs) of primary cilia‐related genes and outcome after the first‐line chemotherapy was explored by the Cox regression model. Expression qualitative trait locus (eQTL) analysis was performed to explore the impact of SNPs on gene expression. Tumor Immune Estimation Resource and TISIDB databases were used for investigating the relevance between ODF2L and tumor infiltration immune cells and immunomodulators.ResultsWe identified that rs4288473 C allele of ODF2L had poor progression‐free survival (PFS) and overall survival (OS) of CRC patients in the additive model (adjusted HRPFS = 1.39, 95% CI = 1.14–1.70, p = 1.36 × 10−3, and adjusted HROS = 1.31, 95% CI = 1.03–1.65, p = 2.62 × 10−2). The stratified analysis indicated that rs4288573 CC/CT genotype was involved with poor prognosis in the irinotecan‐treated subgroup (PPFS = 1.03 × 10−2, POS = 3.29 × 10−3). Besides, ODF2L mRNA expression level was notably up‐regrated in CRC tissues. The C allele of rs4288573 was notably related to higher ODF2L mRNA expression levels based on eQTL analysis. Functionally, knockdown of ODF2L inhibited cell proliferation and decrease the chemoresistance of HCT‐116 and DLD‐1 cells to irinotecan.ConclusionOur study indicates that rs4288573 in ODF2L is a potential predictor of the chemotherapy prognosis of CRC.

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Loss of primary cilia occurs early in breast cancer development

Cited by 123 publications

References 60 publications

Wnt Signaling Inhibits the Growth of Primary Cilia and Activates CyclinD1, Snail and VEGFA Expression in Breast Cancer Cell Line MDA-MB-231

Wnt Signaling Inhibits the Growth of Primary Cilia and Activates CyclinD1, Snail and VEGFA Expression in Breast Cancer Cell Line MDA-MB-231

Primary Cilium-Mediated Crosstalk of Signaling Cascades in Ciliogenesis: Implications for Tumorigenesis and Senescence

Genetic variants in primary cilia‐related genes associated with the prognosis of first‐line chemotherapy in colorectal cancer

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