The hedgehog pathway in triple‐negative breast cancer

Habib, Joyce G.; O’Shaughnessy, Joyce

doi:10.1002/cam4.833

Cited by 106 publications

(96 citation statements)

References 145 publications

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“…Where, SKP1 gene encodes S-phase kinase-associated protein 1 which is an essential component of SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, and mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction, and transcription. 42 Noman et al, 43 quantified the expression pattern on several genes of interest including GLI3 obtained from RNA-seq data of BC samples, TCGA repository. 35 S-phase kinase-associated protein 2 is an enzyme encoded by SKP2 gene.…”

Section: Discussionmentioning

confidence: 99%

Integrated network analysis and machine learning approach for the identification of key genes of triple‐negative breast cancer

Naorem

Venkatesan

2018

J of Cellular Biochemistry

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Triple‐negative breast cancer (TNBC) has attracted more attention compared with other breast cancer subtypes due to its aggressive nature, poor prognosis, and chemotherapy remains the mainstay of treatment with no other approved targeted therapy. Therefore, the study aimed to discover more promising therapeutic targets and investigating new insights of biological mechanism of TNBC. Six microarray data sets consisting of 463 non‐TNBC and 405 TNBC samples were mined from Gene Expression Omnibus. The data sets were integrated by meta‐analysis and identified 1075 differentially expressed genes. Protein‐protein interaction network was constructed which consists of 486 nodes and 1932 edges, where 29 hub genes were obtained with high topological measures. Further, 16 features (hub genes), 12 upregulated (AURKB, CCNB2, CDC20, DDX18, EGFR, ENO1, MYC, NUP88, PLK1, PML, POLR2F, and SKP2) and four downregulated ( CCND1, GLI3, SKP1, and TGFB3) were selected through machine learning correlation based feature selection method on training data set. A naïve Bayes based classifier built using the expression profiles of 16 features (hub genes) accurately and reliably classify TNBC from non‐TNBC samples in the validation test data set with a receiver operating curve of 0.93 to 0.98. Subsequently, Gene Ontology analysis revealed that the hub genes were enriched in mitotic cell cycle processes and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that they were enriched in cell cycle pathways. Thus, the identified key hub genes and pathways highlighted in the study would enhance the understanding of molecular mechanism of TNBC which may serve as potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Integrated network analysis and machine learning approach for the identification of key genes of triple‐negative breast cancer

Naorem

Venkatesan

2018

J of Cellular Biochemistry

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“…The molecular function of Hh protein is achieved by interacting with transmembrane protein, Patched (PTCH), which constitutively represses Hh pathway activity through its interaction with a transmembrane protein Smoothened (SMO). SMO has been suggested to be aberrantly expressed in BCSCs . This signaling pathway has been shown to influence growth, invasion, and metastasis of breast, prostatic, pancreatic, and brain malignancies both in vitro and in vivo .…”

Section: Deregulated Signaling Pathways In Bcscmentioning

confidence: 99%

Breast cancer stem cells as last soldiers eluding therapeutic burn: A hard nut to crack

Nilendu

Kumar

et al. 2017

Intl Journal of Cancer

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Cancer stem cells (CSCs) are found in many cancer types, including breast carcinoma. Breast cancer stem cells (BCSCs) are considered as seed of cancer formation and they are associated with metastasis and genotoxic drug resistance. Several studies highlighted the presence of BCSCs in tumor microenvironment and they are accentuated with several carcinoma events including metastasis and resistance to genotoxic drugs and they also rebound after genotoxic burn. Stemness properties of a small population of cells in carcinoma have provided clues regarding the role of tumor microenvironment in tumor pathophysiology. Hence, insights in cancer stem cell biology with respect to molecular signaling, genetics and epigenetic behavior of CSCs have been used to modulate tumor drug resistance due to genotoxic drugs and signaling protein inhibitors. This review summarizes major scientific breakthroughs in understanding the contribution of BCSCs towards tumor's capability to endure destruction inflicted by molecular as well as genotoxic drugs.

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“…[Oren and Smith, ]. Hh pathway is essential for the maintenance of CSCs in various human cancers including breast [Habib and O'Shaughnessy, ; Zhao et al, ] pancreatic [Lee et al, ; Wang et al, ] gastric [Chong et al, ; Ertao et al, ] Hence, Hh signaling is responsible for the treatment resistance of cancer cells. Thus, inhibitors that obstruct any step of the signaling pathway may result in the depletion of CSCs and hence, overcome the treatment resistance.…”

Section: Approaches Toward Cancer Stem Cell Therapeuticsmentioning

confidence: 99%

Breast Cancer Stem Cell Therapeutics, Multiple Strategies Versus Using Engineered Mesenchymal Stem Cells With Notch Inhibitory Properties: Possibilities and Perspectives

Bose

Sen

2017

J of Cellular Biochemistry

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Relapse cases of cancers are more vigorous and difficult to control due to the preponderance of cancer stem cells (CSCs). Such CSCs that had been otherwise dormant during the first incidence of cancer gradually appear as radiochemoresistant cancer cells. Hence, cancer therapeutics aimed at CSCs would be an effective strategy for mitigating the cancers during relapse. Alternatively, CSC therapy can also be proposed as an adjuvant therapy, along-with the conventional therapies. As regenerative stem cells (RSCs) are known for their trophic effects, anti-tumorogenicity, and better migration toward an injury site, this review aims to address the use of adult stem cells such as dental pulp derived; cord blood derived pure populations of regenerative stem cells for targeting CSCs. Indeed, pro-tumorogenicity of RSCs is of concern and hence has also been dealt with in relation to breast CSC therapeutics. Furthermore, as notch signaling pathways are upregulated in breast cancers, and anti-notch antibody based and sh-RNA based therapies are already in the market, this review focuses the possibilities of engineering RSCs to express notch inhibitory proteins for breast CSC therapeutics. Also, we have drawn a comparison among various possibilities of breast CSC therapeutics, about, notch1 inhibition. J. Cell. Biochem. 119: 141-149, 2018. © 2017 Wiley Periodicals, Inc.

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The hedgehog pathway in triple‐negative breast cancer

Cited by 106 publications

References 145 publications

Integrated network analysis and machine learning approach for the identification of key genes of triple‐negative breast cancer

Integrated network analysis and machine learning approach for the identification of key genes of triple‐negative breast cancer

Breast cancer stem cells as last soldiers eluding therapeutic burn: A hard nut to crack

Breast Cancer Stem Cell Therapeutics, Multiple Strategies Versus Using Engineered Mesenchymal Stem Cells With Notch Inhibitory Properties: Possibilities and Perspectives

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