Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells

Tavera-Mendoza, Luz E.; Westerling, Thomas; Libby, Eric; Marusyk, Andriy; Cato, Laura; Cassani, Raymundo; Cameron, Lisa; Ficarro, Scott B.; Marto, Jarrod A.; Klawitter, Jelena; Brown, Myles

doi:10.1073/pnas.1615015114

Cited by 101 publications

(89 citation statements)

References 52 publications

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“…VDR was shown to downregulate autophagy via constitutive LC3B repression and this repression appears to be abrogated by vitamin D treatment. This abrogation of LC3B repression, together with the upregulation of transcription of Atg defines the regulatory role of vitamin D in autophagy in the breast cancer model used …”

Section: Whole Cell Proteomics Analysismentioning

confidence: 86%

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Proteomics Insights into Autophagy

et al. 2017

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Autophagy, a conserved cellular process by which cells recycle their contents either to maintain basal homeostasis or in response to external stimuli, has for the past two decades become one of the most studied physiological processes in cell biology. The 2016 Nobel Prize in Medicine and Biology awarded to Dr. Ohsumi Yoshinori, one of the first scientists to characterize this cellular mechanism, attests to its importance. The induction and consequent completion of the process of autophagy results in wide ranging changes to the cellular proteome as well as the secretome. MS-based proteomics affords the ability to measure, in an unbiased manner, the ubiquitous changes that occur when autophagy is initiated and progresses in the cell. The continuous improvements and advances in mass spectrometers, especially relating to ionization sources and detectors, coupled with advances in proteomics experimental design, has made it possible to study autophagy, among other process, in great detail. Innovative labeling strategies and protein separation techniques as well as complementary methods including immuno-capture/blotting/staining have been used in proteomics studies to provide more specific protein identification. In this review, we will discuss recent advances in proteomics studies focused on autophagy.

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Section: Whole Cell Proteomics Analysismentioning

confidence: 86%

“…A recent proteomics study by Tavera‐Mendoza et al. also showed autophagy induction by vitamin D in luminal‐like breast cancer cells as well as anti‐proliferative effects . Tavera‐Mendoza et al.…”

Section: Whole Cell Proteomics Analysismentioning

confidence: 92%

Proteomics Insights into Autophagy

et al. 2017

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“…1 Despite progress in breast cancer research, it is a complex disease, and the genetic and molecular mechanisms responsible remain unclear. 2,3 Thus, an understanding of the genetic events underlying breast cancer and the discovery of new biomarkers are needed.…”

Section: Funding Informationmentioning

confidence: 99%

“…Breast cancer is considered to be the most common malignancy among women globally, with an estimated 1.7 million cases diagnosed and 52 1900 deaths in 2012 . Despite progress in breast cancer research, it is a complex disease, and the genetic and molecular mechanisms responsible remain unclear . Thus, an understanding of the genetic events underlying breast cancer and the discovery of new biomarkers are needed.…”

Section: Introductionmentioning

confidence: 99%

Prognostic implications of fibroblast growth factor receptor 4 polymorphisms in primary breast cancer

Wei

You

Sun

et al. 2018

Molecular Carcinogenesis

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Fibroblast growth factor receptor 4 (FGFR4) belongs to the receptor tyrosine kinase (RTK) family, and FGFR4 polymorphisms have been implicated in both normal development and cancer, including breast cancer. In the present study, we investigated correlations between polymorphisms in FGFR4 and breast cancer prognosis. The FGFR4 SNPs rs1966265 and rs351855 were genotyped in 747 breast cancer patients using the SNaPshot method. FGFR4 protein expression was detected by immunohistochemistry in 339 samples. SNP rs351855 was correlated with FGFR4 protein expression under dominant and co-dominant models. Lymph node metastasis (LNM), ER (estrogen receptor) status, and molecular subtype were associated with high FGFR4 expression. Univariate analysis revealed rs351855 (CC/CT: P = 0.027, CC/TT: P < 0.001, CC/CT + TT: P = 0.005) to be a prognostic predictor, and multivariate analysis indicated rs351855 (CC/TT: P = 0.005) to be an independent prognostic factor. Kaplan-Meier survival analysis showed that high FGFR4 protein expression was associated with a poor prognosis. SNP rs351855 was correlated with worse outcomes, with a dose-dependent effect. The results of this study show that FGFR4 SNP rs351855 is associated with up-regulation of FGFR4 protein expression and a worse prognosis in breast cancer.

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“…Its dysfunction has been linked to a wide range of diseases including cancer. Previous studies have shown that VD and its analogs can trigger autophagic death in many cancer cells . SFN can also initiate autophagy in several cell types .…”

Section: Discussionmentioning

confidence: 98%

The Prevention of a High Dose of Vitamin D or Its Combination with Sulforaphane on Intestinal Inflammation and Tumorigenesis in Apc^1638N Mice Fed a High‐Fat Diet

Frederick

Jin

et al. 2018

Molecular Nutrition Food Res

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Scope The previous study shows that obesity‐promoted inflammation is responsible for the activation of the intestinal tumorigenic Wnt‐signaling. The present study aims to test a dietary strategy, dietary supplementation with a high dose of vitamin D (VD) or its combination with sulforaphane (SFN) to inhibit intestinal inflammation and obesity‐associated tumorigenesis. Methods and results Apc1638N mice are randomly divided into four groups: LF, a low‐fat diet (10 kcal% fat) with 200 IU VD; HF, a high‐fat diet (60 kcal% fat) with 200 IU VD; HFD, a high‐fat diet with 5000 IU VD; and HFDS, a high‐fat diet plus 5000 IU VD and 0.23 g SFN per ≈4000 kcal. VD administration decreased tumor incidence and size, and the co‐administration with SFN (HFDS) magnified the effects. Inflammation and Wnt‐signaling are suppressed by VD. The addition of SFN decreased the activity of histone deacetylase (HDAC) and increased autophagy. Conclusion The administration of VD, at 5000 IU level, exerts an anti‐inflammatory property and leads to suppressed intestinal Wnt‐signaling and tumorigenesis in obese mice. The molecular function of SFN on a high dose of VD supplementation, although displayed on the inhibition of HDAC and the activation of autophagy, needs further investigation.

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Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells

Cited by 101 publications

References 52 publications

Proteomics Insights into Autophagy

Proteomics Insights into Autophagy

Prognostic implications of fibroblast growth factor receptor 4 polymorphisms in primary breast cancer

The Prevention of a High Dose of Vitamin D or Its Combination with Sulforaphane on Intestinal Inflammation and Tumorigenesis in Apc^1638N Mice Fed a High‐Fat Diet

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Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells

Cited by 101 publications

References 52 publications

Proteomics Insights into Autophagy

Proteomics Insights into Autophagy

Prognostic implications of fibroblast growth factor receptor 4 polymorphisms in primary breast cancer

The Prevention of a High Dose of Vitamin D or Its Combination with Sulforaphane on Intestinal Inflammation and Tumorigenesis in Apc1638N Mice Fed a High‐Fat Diet

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The Prevention of a High Dose of Vitamin D or Its Combination with Sulforaphane on Intestinal Inflammation and Tumorigenesis in Apc^1638N Mice Fed a High‐Fat Diet