VWCE Functions as a Tumor Suppressor in Breast Cancer Cells

Zhang, Dan; Wan, Lei; Yang, Fan; Liu, Wenlan; Liu, Litao; He, Shengnan; Xie, Ni

doi:10.3389/fonc.2020.586342

Cited by 3 publications

(3 citation statements)

References 33 publications

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“…Furthermore, there exist studies associating this gene with diverse types of neoplasms [ 25 ]. For instance, it was found to be downregulated in breast and prostate cancers, where it functions as a tumor suppressor [ 26 , 27 ]. Interestingly, another project report mentioned the observation of VWCE overexpression in cervical cancer [ 28 ], which aligns with our findings.…”

Section: Resultsmentioning

confidence: 99%

Gene Expression Analysis for Uterine Cervix and Corpus Cancer Characterization

Almorox,

Antequera,

Rojas

et al. 2024

Genes

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The analysis of gene expression quantification data is a powerful and widely used approach in cancer research. This work provides new insights into the transcriptomic changes that occur in healthy uterine tissue compared to those in cancerous tissues and explores the differences associated with uterine cancer localizations and histological subtypes. To achieve this, RNA-Seq data from the TCGA database were preprocessed and analyzed using the KnowSeq package. Firstly, a kNN model was applied to classify uterine cervix cancer, uterine corpus cancer, and healthy uterine samples. Through variable selection, a three-gene signature was identified (VWCE, CLDN15, ADCYAP1R1), achieving consistent 100% test accuracy across 20 repetitions of a 5-fold cross-validation. A supplementary similar analysis using miRNA-Seq data from the same samples identified an optimal two-gene miRNA-coding signature potentially regulating the three-gene signature previously mentioned, which attained optimal classification performance with an 82% F1-macro score. Subsequently, a kNN model was implemented for the classification of cervical cancer samples into their two main histological subtypes (adenocarcinoma and squamous cell carcinoma). A uni-gene signature (ICA1L) was identified, achieving 100% test accuracy through 20 repetitions of a 5-fold cross-validation and externally validated through the CGCI program. Finally, an examination of six cervical adenosquamous carcinoma (mixed) samples revealed a pattern where the gene expression value in the mixed class aligned closer to the histological subtype with lower expression, prompting a reconsideration of the diagnosis for these mixed samples. In summary, this study provides valuable insights into the molecular mechanisms of uterine cervix and corpus cancers. The newly identified gene signatures demonstrate robust predictive capabilities, guiding future research in cancer diagnosis and treatment methodologies.

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Section: Resultsmentioning

confidence: 99%

Gene Expression Analysis for Uterine Cervix and Corpus Cancer Characterization

Almorox,

Antequera,

Rojas

et al. 2024

Genes

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show abstract

“…Upon addition of TGF-β1, the expression of most of these cell type-associated genes was dampened. Notably, some specific genes such as SPON2 , a gene associated with enterocytes and CRC progression (24), PAX6 , encoding a TF associated with enteroendocrine differentiation (25), and the goblet cell-associated gene KRT7 , which has been linked to metastasis (26), were specifically upregulated in basal media with TGF-β1 ( Supplementary Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

AggressiveKRASmutations direct TGF-β response towards partial EMT in patient-derived colorectal cancer tumoroids

Mair,

König,

Mijović

et al. 2024

Preprint

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Transforming growth factor beta (TGF-β) exhibits complex and context-dependent cellular responses. While it mostly induces tumor-suppressive effects in early stages of tumorigenesis, its tumor promoting properties are evident in advanced disease. This TGF-β duality is still not fully understood, and whether TGF-β supports invasion and metastasis by influencing cancer cells directly, or rather through the stromal tumor compartment remains a matter of debate. Here, we utilized a library of colorectal cancer (CRC) patient-derived tumoroids (PDTs), representing a spectrum of tumor stages, to study cancer cell-specific responses to TGF-β. Using medium conditions allowing for the differentiation of PDTs, we observed TGF-β induced tumor-suppressive effects in early-stage tumoroids. PDTs with TGF-β pathway mutations or PDTs derived from metastatic tumors were insensitive to the treatment. Notably, one tumoroid line harboring an atypicalKRASQ22Kmutation underwent partial epithelial-to-mesenchymal transition (EMT), associated with morphological changes and increased invasiveness. On a molecular level, this was accompanied by elevated expression of mesenchymal genes, as well as deregulation of pathways associated with matrix remodeling and cell adhesion. Our results suggest that tumor cell intrinsic responses to TGF-β are critical in determining its tumor-suppressive or -promoting effects.

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“…However, detailed insights into the regulatory mechanism require further structural evidence. VWCE has been reported to function as a tumor suppressor in breast cancer via the induction of WDR1 expression 15 . It has also been reported to act as an oncogene in hepatocellular carcinoma by modulating the β-catenin pathway 12 .…”

Section: Discussionmentioning

confidence: 99%

VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes

Zhao,

Guan,

et al. 2023

Nat Commun

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The mechanistic target of rapamycin complex 1 (mTORC1) is a crucial regulator of cell growth. It senses nutrient signals and adjusts cellular metabolism accordingly. Deregulation of mTORC1 has been associated with metabolic diseases, cancer, and aging. Amino acid signals are transduced to mTORC1 through sensor proteins and two protein complexes named GATOR1 and GATOR2. In this study, we identify VWCE (von Willebrand factor C and EGF domains) as a negative regulator of amino acid-dependent mTORC1 signaling. Knockdown of VWCE promotes mTORC1 activity even in the absence of amino acids. VWCE interacts with the KICSTOR complex to facilitate the recruitment of GATOR1 to the lysosomes. Bioinformatic analysis reveals that expression of VWCE is reduced in prostate cancer. More importantly, overexpression of VWCE inhibits the development of prostate cancer. Therefore, VWCE may serve as a potential therapeutic target for the treatment of prostate cancers.

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VWCE Functions as a Tumor Suppressor in Breast Cancer Cells

Cited by 3 publications

References 33 publications

Gene Expression Analysis for Uterine Cervix and Corpus Cancer Characterization

Gene Expression Analysis for Uterine Cervix and Corpus Cancer Characterization

AggressiveKRASmutations direct TGF-β response towards partial EMT in patient-derived colorectal cancer tumoroids

VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes

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