Oral epithelial stem cells—Implications in normal development and cancer metastasis

Papagerakis, Silvana; Pannone, Giuseppe; Zheng, Li; About, Imad; Taqi, Nawar; Nguyen, Nghia P.T.; Matossian, Margarite D.; McAlpin, Blake; Santoro, Angela; McHugh, Jonathan B.; Prince, Mark; Papagerakis, Pétros

doi:10.1016/j.yexcr.2014.04.021

Cited by 43 publications

(30 citation statements)

References 202 publications

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“…The phenotype of IF1-cells is compatible with the inhibition of cell migration and the maintenance of the ECM. Consistently, members of the Serpin B clade are overexpressed in IF1-cells being some of its members directly related with suppression of migration and invasion in breast cancer (47), whereas its downregulation is associated with the aggressiveness of squamous cell carcinomas (48, 49). On the other hand, (i) ACTA2 which has been related to increased cell motility in breast cancer and other cancer types (50, 51), (ii) POSTN , a protein secreted by cancer cells that has been described to facilitate cell motility and was recently purposed as an interesting target for prevention and treatment of breast tumor metastasis (52, 53), and (iii) VCAN , known to enhance tumorigenesis and cell mobility, invasion, and survival of breast tumors (54), are all dramatically silenced in IF1-overexpressing breast cancer cells.…”

Section: Discussionmentioning

confidence: 85%

Overexpression of the ATPase Inhibitory Factor 1 Favors a Non-metastatic Phenotype in Breast Cancer

et al. 2017

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Partial suppression of mitochondrial oxidative phosphorylation and the concurrent activation of aerobic glycolysis is a hallmark of proliferating cancer cells. Overexpression of the ATPase inhibitory factor 1 (IF1), an in vivo inhibitor of the mitochondrial ATP synthase, is observed in most prevalent human carcinomas favoring metabolic rewiring to an enhanced glycolysis and cancer progression. Consistently, a high expression of IF1 in hepatocarcinomas and in carcinomas of the lung, bladder, and stomach and in gliomas is a biomarker of bad patient prognosis. In contrast to these findings, we have previously reported that a high expression level of IF1 in breast carcinomas is indicative of less chance to develop metastatic disease. This finding is especially relevant in the bad prognosis group of patients bearing triple-negative breast carcinomas. To investigate the molecular mechanisms that underlie the differential behavior of IF1 in breast cancer progression, we have developed the triple-negative BT549 breast cancer cell line that overexpresses IF1 stably. When compared to controls, IF1-cells partially shut down respiration and enhance aerobic glycolysis. Transcriptomic analysis suggested that migration and invasion were specifically inhibited in IF1-overexpressing breast cancer cells. Analysis of gene expression by qPCR and western blotting indicate that IF1 overexpression supports the maintenance of components of the extracellular matrix (ECM) and E-cadherin concurrently with the downregulation of components and signaling pathways involved in epithelial to mesenchymal transition. The overexpression of IF1 in breast cancer cells has no effect in the rates of cellular proliferation and in the cell death response to staurosporine and hydrogen peroxide. However, the overexpression of IF1 significantly diminishes the ability of the cells to grow in soft agar and to migrate and invade when compared to control cells. Overall, the results indicate that IF1 overexpression despite favoring a metabolic phenotype prone to cancer progression in the specific case of breast cancer cells also promotes the maintenance of the ECM impeding metastatic disease. These findings hence provide a mechanistic explanation to the better prognosis of breast cancer patients bearing tumors with high expression level of IF1.

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Section: Discussionmentioning

confidence: 85%

Overexpression of the ATPase Inhibitory Factor 1 Favors a Non-metastatic Phenotype in Breast Cancer

et al. 2017

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“…It is also involved in maintenance of normal skin structure and function, through control of the permeability barrier function (Demehri et al, 2009a; Demehri et al, 2009b; Dumortier et al, 2010). This pathway appears to play an equally important regulatory role in the oral (Papagerakis et al, 2014), esophageal (Croagh et al, 2014) and bronchial epithelia (Garcia Campelo et al, 2011). …”

Section: Squamous Differentiation Networkmentioning

confidence: 99%

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

2016

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SUMMARY Squamous cell carcinomas (SCCs) represent the most frequent human solid tumors and a major cause of cancer mortality. These highly heterogeneous tumors arise from closely interconnected epithelial cell populations with intrinsic self-renewal potential inversely related to the stratified differentiation program. SCCs can also originate from simple or pseudo-stratified epithelia through activation of quiescent cells and/or a switch in cell fate determination. Here, we focus on specific determinants implicated in the development of SCCs by recent large-scale genomic, genetic and epigenetic studies and complementary functional analysis. This evidence indicates that SCCs from various body sites, while clinically treated as separate entities, have common determinants, pointing to a unified perspective of the disease and potential new avenues for prevention and treatment.

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“…These cells are able to differentiate into the different cell types of the oral mucosa and are responsible for tissue repair after damage. Although the precise location of these cells has not yet been defined, they probably reside within the basal layer, where they proliferate at a very slow rate [4][5][6]. The long-term persistence of these cells within the epithelium explains why they are more susceptible to accumulate multiple mutations and therefore to undergo malignant transformation (which requires at least 5 mutations on average [5,7]).…”

Section: The Concept Of Field Cancerizationmentioning

confidence: 99%

Open questions and novel concepts in oral cancer surgery

Tirelli

Zacchigna

Biasotto

et al. 2015

Eur Arch Otorhinolaryngol

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The persistence of cancerous cells after surgery in oral squamous cell carcinoma (OSCC) represents a major challenge, as it often leads to local recurrences and secondary primary tumors, which are eventually responsible for a large proportion of deaths. This persistence is currently evaluated by histological analyses. In this review we discuss some important pitfalls of the histopathological analysis, such as margin evaluation, specimen shrinkage and T staging. In addition, we critically analyze the appropriateness of current surgical techniques in relation to the concept of field cancerization. Finally, we describe some novel imaging and molecular approaches, which might be useful in tailoring surgical resections and encourage the use of OSCC animal models to explore and provide proof of concept of the feasibility and potential clinical utility of innovative surgical protocols.

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Oral epithelial stem cells—Implications in normal development and cancer metastasis

Cited by 43 publications

References 202 publications

Overexpression of the ATPase Inhibitory Factor 1 Favors a Non-metastatic Phenotype in Breast Cancer

Overexpression of the ATPase Inhibitory Factor 1 Favors a Non-metastatic Phenotype in Breast Cancer

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

Open questions and novel concepts in oral cancer surgery

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