Stem Cells and Cancer: The Molecular Mechanisms of Cancer Stemness

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Cell Biology and Tissue Engineering".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 3692

Special Issue Editors

Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada
Interests: functional genomics; functional proteomics; genetic interactions; signal transduction; system biology; cancer biology; cancer stemness

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Guest Editor
Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada
Interests: cancer biology; targeted cancer therapy; cell stress response; gene therapy; cancer genetics; pediatric cancer; cancer immunotherapy
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Oncology, University of Alberta, Edmonton, AB T6G 2H7, Canada
Interests: genetics-gene therapy; genetics; stem cell; cancer genetics; cancer biology; molecular biology; genes intractions; behaviral genetics

Special Issue Information

Dear Colleagues,

If a cancerous tumor is a tissue, it should have its own stem cells. The idea that cancer can originate from stem cells dates back to the mid-19th century, when father pathologists observed malignant cancer tissue under the microscope and noticed the similarity between cancer and embryonic tissues. They suggested that cancers arise from embryonic cells. This concept was later formalized by Julius Cohnheim when he published his “embryonal rest” theory in 1875. The theory stated that embryonic remains from developmental stages lie dormant in the adult tissues but could be activated to form cancer. More than 120 years after the introduction of embryonal rest theory, Dominique Bonnet and John Dick at the University of Toronto confirmed that leukemia cells originated from a small subpopulation (less than 1 in 10,000) of hematopoietic stem cells. Since this discovery, so far, cancer stem cells (CSC) have been identified in several solid tumors including brain, breast, ovary, colon, lung, kidney, pancreas, melanoma, prostate, gastric, head and neck and non-melanoma skin cancers. CSCs are defined as a small subset of cells within a tumor that share many behaviors and features of both cancer and normal stem cells, including pluripotency, self-renewal, slow growth and the ability to differentiate to multiple tumor cells. CSCs are known to be responsible for cancer metastasis, therapy resistance and relapse since they can survive anti-cancer therapies and generate new tumors. Although the existence and origins of CSCs are still under debate, some believe that targeting CSCs is the key to cancer therapy.

In this Special Issue of Life, we invite researchers to share with us new insights into the molecular and cellular mechanism of stemness in cancer and to improve our understanding of CSC biology.

Dr. Babak Nami
Dr. Hamid Maadi
Dr. Maryam Hejazi
Guest Editors

Manuscript Submission Information

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Keywords

  • cancer stem cell
  • tumor-initiating cell
  • tumor heterogeneity and plasticity
  • signaling pathway
  • epithelial–mesenchymal transition

Published Papers (1 paper)

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Research

12 pages, 1830 KiB  
Article
Epigenetic Silencing of HER2 Expression during Epithelial-Mesenchymal Transition Leads to Trastuzumab Resistance in Breast Cancer
by Babak Nami, Avrin Ghanaeian, Corbin Black and Zhixiang Wang
Life 2021, 11(9), 868; https://doi.org/10.3390/life11090868 - 24 Aug 2021
Cited by 7 | Viewed by 3018
Abstract
HER2 receptor tyrosine kinase (encoded by the ERBB2 gene) is overexpressed in approximately 25% of all breast cancer tumors (HER2-positive breast cancers). Resistance to HER2-targeting therapies is partially due to the loss of HER2 expression in tumor cells during treatment. However, little is [...] Read more.
HER2 receptor tyrosine kinase (encoded by the ERBB2 gene) is overexpressed in approximately 25% of all breast cancer tumors (HER2-positive breast cancers). Resistance to HER2-targeting therapies is partially due to the loss of HER2 expression in tumor cells during treatment. However, little is known about the exact mechanism of HER2 downregulation in HER2-positive tumor cells. Here, by analyzing publicly available genomic data we investigate the hypothesis that epithelial-mesenchymal transition (EMT) abrogates HER2 expression by epigenetic silencing of the ERBB2 gene as a mechanism of acquired resistance to HER2-targeted therapies. As result, HER2 expression was found to be positively and negatively correlated with the expression of epithelial and mesenchymal phenotype marker genes, respectively. The ERBB2 chromatin of HER2-high epithelial-like breast cancer cells and HER2-low mesenchymal-like cells were found to be open/active and closed/inactive, respectively. Decreased HER2 expression was correlated with increased EMT phenotype, inactivated chromatin and lower response to lapatinib. We also found that induction of EMT in the HER2-positive breast cancer cell line BT474 resulted in downregulated HER2 expression and reduced trastuzumab binding. Our results suggest that ERBB2 gene silencing by epigenetic regulation during EMT may be a mechanism of de novo resistance of HER2-positive breast cancer cells to trastuzumab and lapatinib. Full article
(This article belongs to the Special Issue Stem Cells and Cancer: The Molecular Mechanisms of Cancer Stemness)
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