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Cited by 28Mechanisms of cancer metastasisVirus-based gene therapy researchCancer Cells and Metastasis

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

A novel gammaretroviral shuttle vector insertional mutagenesis screen identifies SHARPIN as a breast cancer metastasis gene and prognostic biomarker

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Bii, Victor M., Rae, Dustin T., Trobridge, Grant D.·2015·Oncotarget
DOI 10.18632/oncotarget.6232PMC PMC4741842
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Abstract

// Victor M. Bii 1 , Dustin T. Rae 1 and Grant D. Trobridge 1,2 1 Washington State University College of Pharmacy, WSU Spokane, Spokane, WA, USA 2 School of Molecular Biosciences, Washington State University, Pullman, Washington, USA Correspondence to: Grant D. Trobridge, email: // Keywords : insertional mutagenesis screen, breast cancer, gammaretroviral vector (γRV), metastasis, prognostic biomarker, Chromosome Section Received : October 02, 2015 Accepted : October 14, 2015 Published : October 25, 2015 Abstract Breast cancer (BC) is the second leading cause of malignancy among U.S. women. Metastasis results in a poor prognosis and increased mortality, but the molecular mechanisms by which metastatic tumors occur are not well understood. Identifying the genes that drive the metastatic process could provide targets for improved therapy and biomarkers to improve BC patient outcomes. Using a forward mutagenesis screen, BC cells mutagenized with a replication-incompetent gammaretroviral vector (γRV) were xenotransplanted into the mammary fat pad of immunodeficient mice. In this approach the vector provirus dysregulates nearby genes, providing a selective advantage to transduced cells to form metastases. Metastatic tumors were analyzed for proviral integration sites to identify nearby candidate metastasis genes. The γRV has a transgene cassette that allows for rescue in bacteria and rapid identification of vector integration sites. Using this approach, we identified the previously described metastasis gene WWTR1 (TAZ), and three other novel candidate metastasis genes including SHARPIN. SHARPIN was independently validated in vivo as a BC metastasis gene. Analysis of patient data showed that SHARPIN expression predicts metastasis-free survival after adjuvant therapy. Our approach has broad potential to identify genes involved in oncogenic processes for BC and other cancers. We show here it can identify both known (WWTR1) and novel (SHARPIN) BC metastasis genes.

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  • SHARPIN gene amplification and protein overexpression has been observed in several human cancer types.

    “SHARPIN gene amplification and protein overexpression has been observed in several human cancer types (Fig. S1A) (Bii et al., 2015, De Melo & Tang, 2015, He et al., 2010, Jung et al., 2010).”

    From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Bii et al., 2015

    The Results section reports SHARPIN overexpression in breast cancer tumors and examines genetic alterations, including amplification, in breast cancer samples. The Discussion also describes SHARPIN up-regulation in prostate cancer. These passages do not establish SHARPIN gene amplification and protein overexpression across several human cancer types; the reported tumor-expression analysis measures mRNA, not protein. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • SHARPIN gene is amplified in a variety of human cancers.

    “SHARPIN gene is amplified, and at the protein level it is overexpressed in a variety of human cancers (Fig. S1A)”

    From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Bii, Rae et al., 2015

    The Results section, “Candidate BC metastasis genes are recurrently altered in BC patients” (page unavailable), reports SHARPIN alterations in breast-cancer samples and says the analysis included copy-number amplification. It does not state that the SHARPIN alterations were amplifications or establish amplification across a variety of human cancers. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • SHARPIN protein is overexpressed in a variety of human cancers.

    “SHARPIN gene is amplified, and at the protein level it is overexpressed in a variety of human cancers (Fig. S1A)”

    From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Bii, Rae et al., 2015

    The Results section reports elevated SHARPIN expression in breast-cancer tumors, and the Discussion mentions SHARPIN up-regulation in prostate cancer (page numbers unavailable). But the breast-cancer analysis measured mRNA, and the paper does not establish that SHARPIN protein is overexpressed across a variety of human cancers. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • SHARPIN promotes cancer progression and metastasis.

    “The adaptor protein SHARPIN is involved in a number of cellular processes and promotes cancer progression and metastasis.”

    From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Bii et al., 2015

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Metadata

Authors
Bii, V. M., Rae, D. T., & Trobridge, G. D.
Affiliations
Washington State University Spokane (US)
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2015-10-25
Volume
6
Issue
37
Pages
39507-39520
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.6232
PMC
PMC4741842
OpenAlex
W1852461160
Cited by
28
References
5
Citations by year
2025: 1 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 3
FWCI
1.59
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense (W81XWH-11-1-, W81XWH)
  • National Institutes of Health (W81XWH)
  • National Cancer Institute (CA173598, R15CA173598)
  • National Institute of Allergy and Infectious Diseases (R01AI102672, P01AI097100)
  • DOD Peer Reviewed Cancer Research Program
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
breast cancer metastasis, SHARPIN, gammaretroviral vectors, TAZ, metastasis-associated genes, prognostic factors, metastasis-free survival, proviral integration sites, xenotransplantation, adjuvant therapy
MeSH terms
RNAi Therapeutics, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Animals, Base Sequence, Breast Neoplasms, Genetic Vectors, Humans, Molecular Sequence Data, Neoplasm Metastasis, Prognosis, Transcription Factors, Biomarkers, Tumor, Ubiquitins, Trans-Activators, Gene Expression Regulation, Neoplastic, Mutagenesis, Insertional, Gammaretrovirus, Xenograft Model Antitumor Assays, RNA Interference, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, Kaplan-Meier Estimate

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