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Article

Vitamin C Inhibits Triple-Negative Breast Cancer Metastasis by Affecting the Expression of YAP1 and Synaptopodin 2

1
John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
2
State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
3
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Nutrients 2019, 11(12), 2997; https://doi.org/10.3390/nu11122997
Received: 21 October 2019 / Revised: 21 November 2019 / Accepted: 3 December 2019 / Published: 6 December 2019
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
Vitamin C supplementation has been shown to decrease triple-negative breast cancer (TNBC) metastasis. However, the molecular mechanism whereby vitamin C inhibits metastasis remains elusive. It has been postulated that vitamin C reduces the levels of HIF-1α, the master regulator of metastasis, by promoting its hydroxylation and degradation. Here, we show that vitamin C at 100 µM, a concentration achievable in the plasma in vivo by oral administration, blocks TNBC cell migration and invasion in vitro. The protein level of HIF-1α remains largely unchanged in cultured TNBC cells and xenografts, partially due to its upregulated transcription by vitamin C, suggesting that HIF-1α unlikely mediates the action of vitamin C on metastasis. Vitamin C treatment upregulates the expression of synaptopodin 2 and downregulates the expression of the transcription coactivator YAP1, both genes in the Hippo pathway. The changes in SYNPO2 and YAP1 expression were subsequently validated at mRNA and protein levels in cultured TNBC cells and xenografts. Further experiments showed that vitamin C treatment inhibits F-actin assembly and lamellipodia formation, which correlates with the changes in SYNPO2 and YAP1 expression. Overall, these results suggest that vitamin C inhibits TNBC metastasis by affecting the expression of SYNPO2 and YAP1. Vitamin C may thus have a potential role in the prevention and treatment of TNBC metastasis. View Full-Text
Keywords: vitamin C; triple-negative breast cancer; metastasis; HIF-1α; YAP1; synaptopodin 2; lamellipodia; F-actin; hippo pathway vitamin C; triple-negative breast cancer; metastasis; HIF-1α; YAP1; synaptopodin 2; lamellipodia; F-actin; hippo pathway
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MDPI and ACS Style

Gan, L.; Camarena, V.; Mustafi, S.; Wang, G. Vitamin C Inhibits Triple-Negative Breast Cancer Metastasis by Affecting the Expression of YAP1 and Synaptopodin 2. Nutrients 2019, 11, 2997. https://doi.org/10.3390/nu11122997

AMA Style

Gan L, Camarena V, Mustafi S, Wang G. Vitamin C Inhibits Triple-Negative Breast Cancer Metastasis by Affecting the Expression of YAP1 and Synaptopodin 2. Nutrients. 2019; 11(12):2997. https://doi.org/10.3390/nu11122997

Chicago/Turabian Style

Gan, Liping, Vladimir Camarena, Sushmita Mustafi, and Gaofeng Wang. 2019. "Vitamin C Inhibits Triple-Negative Breast Cancer Metastasis by Affecting the Expression of YAP1 and Synaptopodin 2" Nutrients 11, no. 12: 2997. https://doi.org/10.3390/nu11122997

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