ABCG2-Meditated Multidrug Resistance and Tumor-Initiating Capacity of Side Population Cells from Colon Cancer

Xie, Zhengyuan; Lv, Ke; Xiong, Ying; Guo, Wu-Hua

doi:10.1159/000368842

Cited by 42 publications

(36 citation statements)

References 17 publications

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“…The ATP-binding cassette transporter (ABC) family induces resistance to chemotherapy in several malignancies. 42,49–53 Recently, based on the expression of the ABC family member ABCB5, melanoma cancer stem cells (MCSCs) were identified and it was shown that ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine signaling circuit. 54 Wang et al 50 showed that Panc-1 pancreatic CSCs express high levels of CD133/CD44/Oct4/Nestin compared to Panc-1 cells, are resistant to gemcitabine, and express high levels of P-gp as well as high anti-apoptotic proteins, but exhibit weak proliferative potential.…”

Section: Mechanisms Of Death Resistance In Cancer Stem Cellsmentioning

confidence: 99%

Resistance to Cell Death and Its Modulation in Cancer Stem Cells

2016

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Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs. Several signaling pathways—including the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), maternal embryonic leucine zipper kinase (MELK), NOTCH1, and Wnt/β-catenin—and expression of the CSC markers CD133, CD24, CD44, Oct4, Sox2, Nanog, and ALDH1A1 maintain CSC properties. Studying such pathways may help to understand CSC biology and lead to the development of potential therapeutic interventions to render CSCs more sensitive to cell death triggered by chemotherapy and radiation therapy. Moreover, recent demonstrations of dedifferentiation of differentiated cancer cells into CSC-like cells have created significant complexity in the CSCs hypothesis. Therefore, any successful therapeutic agent or combination of drugs for cancer therapy must eliminate not only CSCs but differentiated cancer cells and the entire bulk of tumor cells. This review article expands on the CSC hypothesis and paradigm with respect to major signaling pathways and effectors that regulate CSC apoptosis resistance. Moreover, selective CSC apoptotic modulators and their therapeutic potential for making tumors more responsive to therapy are discussed. The use of novel therapies, including small-molecule inhibitors of specific proteins in signaling pathways that regulate stemness, proliferation and migration of CSCs, immunotherapy, and noncoding microRNAs may provide better means of treating CSCs.

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Section: Mechanisms Of Death Resistance In Cancer Stem Cellsmentioning

confidence: 99%

Resistance to Cell Death and Its Modulation in Cancer Stem Cells

2016

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“…51,52 and an elevated expression of anti-apoptotic proteins. 4 • As such, CSCs exhibit increased resistance to standard radio-and chemotherapies.…”

Section: Characteristics Of Cancer Stem Cellsmentioning

confidence: 99%

Targeting Cancer Stem Cells—A Renewed Therapeutic Paradigm

Amey¹,

Karnoub

2017

Oncology &Amp; Hematology Review (US)

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Metastasis is often accompanied by radio-and chemotherapeutic resistance to anticancer treatments and is the major cause of death in cancer patients. Better understanding of how cancer cells circumvent therapeutic insults and how disseminated cancer clones generate life-threatening metastases would therefore be paramount to the development of effective therapeutic approaches for clinical management of malignant disease. Mounting reports over the past two decades have provided evidence for the existence of a minor population of highly malignant cells within liquid and solid tumors, which are capable of self-renewing and of regenerating secondary growths with the heterogeneity of the primary tumors from which they derive. These cells, called tumor-initiating cells or cancer stem cells (CSCs) exhibit increased resistance to standard radio-and chemotherapies and appear to have mechanisms that enable them to evade immune surveillance. CSCs are therefore considered to be responsible for systemic residual disease after cancer therapy, as well as for disease relapse. How CSCs develop, the nature of the interactions they establish with their microenvironment, their phenotypic and functional characteristics, as well as their molecular dependencies have all taken center stage in cancer therapy. Indeed, improved understanding of CSC biology is critical to the development of important CSC-based anti-neoplastic approaches that have the potential to radically improve cancer management. Here, we summarize some of the most pertinent elements regarding CSC development and properties, and highlight some of the clinical modalities in current development as anti-CSC therapeutics.

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“…Besides introduced markers listed in Table 1 Apart from in vitro studies, analyzing clinical samples revealed that CD44 could be used in combination with clinicopathological information to improve the OSCC prognosis, since its overexpression, in tumor samples and peripheral blood of OSCC patients, was correlated to poor prognosis LGR5 [152,153] EpCAM [120] BMI1 [119,218] CD24 [122,125] OCT4 [118,119] SOX2 [118,119,[149][150][151] NANOG [118,119] Colon and rectum CD44 [166,[180][181][182][183][184][185][186][187][188][189][190][191][192][193][194][195][196][197][198]200] CD133 [161-165, 171-178, 186-188, 232] ABCG2 [75,158,159] ALDH1 [198,[222][223][224]…”

Section: Oral Cavitymentioning

confidence: 99%

“…One of the first reports on CRC stem-like cells was the isolation of highly proliferative and therapy-resistant SP cells from CRC cell lines [75]. Later results have also introduced SP cells as stem-like CRC cells, due to their high proliferation, invasion, and tumorigenic abilities [158,159]. However, there is a report indicating that sorting for SP cells does not apply to colon CSCs, as both SP and NSP cells were clonogenic in vitro and tumorigenic in vivo and displayed similar differentiation potential and expression pattern for CD133, CD44, OCT4, and ABCG2 [160].…”

Section: Colon and Rectummentioning

confidence: 99%

Cancer stem cells in human digestive tract malignancies

2015

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Digestive tract malignancies, including oral, pharyngeal, esophageal, gastric, and colorectal cancers, are among the top 10 most common cancers worldwide. In spite of using various treatment modalities, cancer patients still suffer from recurrence and metastasis of malignant cells. Cancer stem cells (CSCs) are undifferentiated and highly proliferative malignant cells with unique properties mediated by overexpression of stemness markers, metastasis-related proteins, drug transporters, and DNA repair machinery. Due to their salient characteristics, it has been suggested that CSCs are responsible for tumor initiation, progression, invasion, recurrence, and therapy resistance. Exploring different aspects of CSC biology has fueled a great enthusiasm in designing novel therapeutic strategies to help patients. For instance, identification of markers associated with digestive tract CSCs, such as CD44, CD133, CD24, EpCAM, LGR5, ALDH1, and BMI1, has made it possible to develop more accurate diagnosis approaches. In addition, specifically targeting CSCs by their markers imposes fewer side effects and improves therapeutic outcomes. Here, we focus on the current status of CSC biology in digestive tract cancers, with emphasis on CSC markers, and review achieved progress in eradication of digestive tract CSC cells.

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ABCG2-Meditated Multidrug Resistance and Tumor-Initiating Capacity of Side Population Cells from Colon Cancer

Cited by 42 publications

References 17 publications

Resistance to Cell Death and Its Modulation in Cancer Stem Cells

Resistance to Cell Death and Its Modulation in Cancer Stem Cells

Targeting Cancer Stem Cells—A Renewed Therapeutic Paradigm

Cancer stem cells in human digestive tract malignancies

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