SND1 facilitates the invasion and migration of cervical cancer cells by Smurf1-mediated degradation of FOXA2

Zhan, Fuliang; Zhong, Yanying; Qin, Yulin; Li, Liang; Wu, Wenwen; Yao, Mei-Zhen

doi:10.1016/j.yexcr.2019.111809

Cited by 24 publications

(14 citation statements)

References 29 publications

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“…Consistent with the evidence, we found that OGT and global O-GlcNAcylation levels Recently, it has become clear that O-GlcNAcylation can effectively regulate protein stability and the cross-talk between O-GlcNAcylation and ubiquitylation plays a general role in protein stability regulation (Chu et al, 2020;Makwana, Ryan, et al, 2019). It also has been recently reported that ubiquitination of FOXA2 plays a vital role in the degradation of FOXA2, and promotes the metastasis of cervical cancer cells (Zhan et al, 2020). In our study, we revealed that hyper-O-GlcNAcylation of FOXA2 reduced its stability by…”

Section: Discussionsupporting

confidence: 89%

“…Increasing evidence has shown that FOXA2 expression and activity are regulated by various PTMs (Belaguli et al, 2012;M. Liu et al, 2012;VonMeyenn et al, 2013;Wolfrum et al, 2003;Zhan et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that the regulation of FOXA2 activity is achieved through a variety of posttranscriptional modifications (PTMs). As a downstream responsive nuclear factor of multiple signaling pathways, hormonal and stress-dependent regulation of FOXA2 via phosphorylation, acetylation, and ubiquitination are well established (M. Liu et al, 2012;VonMeyenn et al, 2013;Wolfrum et al, 2003;Zhan et al, 2020). For example, PI3K/AKTinduced phosphorylation of FOXA2 results in its nuclear exclusion and transcriptional inactivation (Wolfrum et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity

Huang

Guo

et al. 2021

Journal Cellular Physiology

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O-GlcNAcylation is a posttranslational modification that regulates numerous nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes, such as transcription, signal transduction, and cell motility.Although increasing evidence has shown that elevated levels of global O-GlcNAcylation are linked to the metastasis in hepatocellular carcinoma (HCC) cells, the underlying mechanism is still ambiguous. In this study, we demonstrated that forkhead box protein A2 (FOXA2), an essential transcription factor for liver homeostasis and HCC developing, was O-GlcNAcylated by O-GlcNAc transferase (OGT) and regulates HCC cells migration and invasion. Opposite FOXA2 and OGT expression tendency were observed in HCC tissues, and lower FOXA2 levels predicted a poor prognosis in HCC patients. The reduction of FOXA2 in HCC cells was found to be inversely correlated with the cellular O-GlcNAcylation and cell migratory ability. Notably, we found that FOXA2 was modified by O-GlcNAcylation and that O-GlcNAcylation activated the ubiquitination degradation of FOXA2 in highly metastatic HCC cells. Although this modification did not affect FOXA2 nuclear localization capability, O-GlcNAcylation on FOXA2 was key for attenuating FOXA2-mediated transcription. O-GlcNAcylation decreased the transcription of FOXA2 downstream target gene E-cadherin and it ultimately promoted O-GlcNAcylation-mediated HCC cell migration and invasion. The results provide insights into the role of O-GlcNAcylation in regulating FOXA2 activity and suggest its important implications in HCC metastasis.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity

Huang

Guo

et al. 2021

Journal Cellular Physiology

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“…Although many imputation methods exist, we considered the most conservative approach was to use the available data without imputation as it is often more robust and is less likely to suffer from any other biases [17]. Many of these 16 proteins have previously been shown to influence metastasis in other cancers, for instance, ACTG1 in liver cancer [18], Immunoglobulin heavy constant gamma 3 (IGHG3) in breast cancer [19], Proteasome subunit alpha type-1 (PSMA1) in colon cancer [20], Ras-related protein Rab-11A (RAB11a) in pancreatic cancer [21], PEBP1 and Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) in hepatocellular carcinoma [22,23], MYH9 in colorectal [24] and ovarian cancer [25], POSTN in melanoma [26], hepatocellular carcinoma [27] and breast cancer [28] and SND1 in breast cancer [29] and cervical cancer [30]. Furthermore, five of these proteins were identified as significantly differentially expressed between PM and PNMs in two NCBI GEO datasets and the gene expression of 6 of these 16 significantly differentially expressed proteins (i.e., EVPL, POSTN, KRT9, MYH9, MYH16 and PEBP1) each had a significant effect on 3-year survival rates in cutaneous melanoma as identified from the TCGA database.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Archived Tissue of Primary Melanoma Identifies Proteins Associated with Metastasis

Shapanis

Lai

Sommerlad

et al. 2020

IJMS

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Formalin-fixed paraffin embedded (FFPE) clinical tissues represent an abundant and unique resource for translational proteomic studies. In the US, melanoma is the 5th and 6th most common cancer in men and women, respectively, affecting over 230,000 people annually and metastasising in 5–15% of cases. Median survival time for distant metastatic melanoma is 6–9 months with a 5-year-survival of < 15%. In this study, 24 primary FFPE tumours which have metastasised (P-M) and 24 primary FFPE tumours which did not metastasise (P-NM) were subjected to proteomic profiling. In total, 2750 proteins were identified, of which 16 were significantly differentially expressed. Analysis of TCGA data demonstrated that expression of the genes encoding for 6 of these 16 proteins had a significant effect on survival in cutaneous melanoma. Pathway analysis of the proteomics data revealed mechanisms likely involved in the process of melanoma metastasis, including cytoskeleton rearrangement, extracellular changes and immune system alterations. A machine learning prediction model scoring an AUC of 0.922, based on these 16 differentially expressed proteins was able to accurately classify samples into P-M and P-NM. This study has identified potential biomarkers and key processes relating to melanoma metastasis using archived clinical samples, providing a basis for future studies in larger cohorts.

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“…Additionally, FOXA2 is downregulated by miR-590-3p in ovarian cancer, which promotes cancer growth and metastasis [ 30 ]. Similarly, FOXA2 has been reported to be a tumor suppressor gene in various cancers and is a target of oncogenes, such as in pancreatic cancer [ 31 ], liver cancer [ 32 ], oral cancer [ 33 , 34 ], and cervical cancer [ 35 ]. On the other hand, FOXA2 has been reported to promote EMT in colon cancer and prostate cancer [ 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

CD44 Promotes Breast Cancer Metastasis through AKT-Mediated Downregulation of Nuclear FOXA2

et al. 2022

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The primary cause of breast cancer mortality is the metastatic invasion of cancerous stem cells (CSC). Cluster of differentiation 44 (CD44) is a well-known CSC marker in various cancers, as well as a key role player in metastasis and relapse of breast cancer. CD44 is a cell-membrane embedded protein, and it interacts with different proteins to regulate cancer cell behavior. Transcription factor forkhead box protein A2 (FOXA2) acts as an important regulator in multiple cancers, including breast cancer. However, the biological significance of CD44-FOXA2 association in breast cancer metastasis remains unclear. Herein, we observed that CD44 expression was higher in metastatic lymph nodes compared to primary tumors using a flow cytometric analysis. CD44 overexpression in breast cancer cell lines significantly promoted cell migration and invasion abilities, whereas the opposite effects occurred upon the knockdown of CD44. The stem cell array analysis revealed that FOXA2 expression was upregulated in CD44 knockdown cells. However, the knockdown of FOXA2 in CD44 knockdown cells reversed the effects on cell migration and invasion. Furthermore, we found that CD44 mediated FOXA2 localization in breast cancer cells through the AKT pathway. Moreover, the immunofluorescence assay demonstrated that AKT inhibitor wortmannin and AKT activator SC79 treatment in breast cancer cells impacted FOXA2 localization. Collectively, this study highlights that CD44 promotes breast cancer metastasis by downregulating nuclear FOXA2.

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SND1 facilitates the invasion and migration of cervical cancer cells by Smurf1-mediated degradation of FOXA2

Cited by 24 publications

References 29 publications

O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity

O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity

Proteomic Profiling of Archived Tissue of Primary Melanoma Identifies Proteins Associated with Metastasis

CD44 Promotes Breast Cancer Metastasis through AKT-Mediated Downregulation of Nuclear FOXA2

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