Stem Cell Self-Renewal and Cancer Cell Proliferation Are Regulated by Common Networks That Balance the Activation of Proto-oncogenes and Tumor Suppressors

Pardal, Ricardo; Molofsky, Anna V.; He, Shirley; Morrison, Sean J.

doi:10.1101/sqb.2005.70.057

Cited by 126 publications

(106 citation statements)

References 97 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…The SV40ER encodes for LT and ST antigens, which are known to inactivate tumor suppressors such as p53, pRb and PP2A (Yang et al, 1991;Ali and DeCaprio, 2001), and recent studies have identified a role for several oncogenes and tumor-suppressor genes in the regulation of stemness properties (Pardal et al, 2005). For example, downregulation of p53 has been associated with increased selfrenewal, and upregulation of stem cell markers, such as Nanog, ABCB1 and CD44 (Jerry et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

et al. 2011

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

et al. 2011

View full text Add to dashboard Cite

“…Imbalance of the expressions of these molecules causes cancer because of self-renewing and progression capabilities. 26,27 Bmi-1 mRNAs and proteins tend to be expressed in well-differentiated/early and lose expression in poorly differentiated/progressed HNSCC (Tables 1-3). Subsequent identification of Bmi-1 protein expression could distinguish early lesions of cancerous tissue from non-cancerous tissues in HNSCCs (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Stem cell self-renewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis

Yamazaki

Mori

Yazawa

et al. 2013

Laboratory Investigation

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) includes both morphological and functional cellular heterogeneity, as would be expected if it arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell; however, stemness molecule expression levels and distribution in HNSCC remain unclear. To clarify this, stemness molecule expressions were determined in HNSCC, as well as their properties and prognosis. Two protooncogenic chromatin regulators, Bmi-1 and high-mobility-group A2 (Hmga2), were identified in 12 pair cases of HNSCC tumor regions by comparison with their non-cancerous background tissues using cDNA microarray. Both Bmi-1 and Hmga2 are known to promote stem cell self-renewal by negatively regulating the expressions of Ink4a and Arf tumor suppressors. Despite similar targets, Bmi-1 protein was expressed in an early cancerous region and HMGA2 protein was expressed in a region showing more progression. Similarly, Bmi1 expression had no significance with regard to overall survival (P ¼ 0.67), whereas HMGA2 expression was associated with decreased overall survival (P ¼ 0.05). Quantitative realtime reverse transcription polymerase chain reaction analyses also correlated with protein levels. These findings suggest that Bmi-1 is an early detection marker to distinguish cancerous from non-cancerous regions, whereas HMGA2 is presumed to be a tumor prognosis marker. Among our HNSCC analyses, these stemness molecules expressed fewer primitive rare cells in the tumor than all other cells in the tumor. HNSCC cells with high expression of stemness molecules partly behave like stem cells. Head and neck squamous cell carcinoma (HNSCC) is typically associated with virus infection, persistent chronic inflammation, and tobacco and alcohol use. Survival rates have changed in the last 40 years because of reductions in these factors; 1 however, the mortality rate remains high because advanced and recurrent locoregional control is difficult in many cases. Better understanding of the biology of HNSCC is required to define relevant targets and to develop novel therapeutic approaches. HNSCCs have both morphological and functional cellular heterogeneity, as would be expected if they arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell. 2 Recently, numerous reports have shown support for the 'cancer stem cell' theory in many types of tumor, including HNSCC. 3,4,5 Acute and chronic myeloid leukemias follow the cancer stem cell model. Both tumors show robustly hematopoietic hierarchical organization in the tumor cells; 6,7 however, for solid cancers such as squamous cell carcinoma, it is not clear how generalizable the cancer stem cell model is. Not all cancer cells have the same capacity to proliferate. 8 In some cancers, most cancer cells appear to have limited ability to proliferate, while in the same tumors, stochastic minority populations of stemness molecules highly expressed in cancer as a 'stem-like cancer' retain the capacity...

show abstract

“…There are several other proteins known to regulate multiple progenitor lineages. Bmi1 and other polycomb proteins repress genes that induce cell death in the hematopoetic lineages, neural stem cells, NC stem cells and cancer stem cells (reviewed by Pardal et al, 2005). Most recently, the transcription factor Zfx has been shown to be required for self-renewal of ES cells and maintenance of adult hematopoietic stem cells (Galan-Caridad et al, 2007).…”

Section: Conservation Of Foxd3 Function In Progenitor Cellsmentioning

confidence: 99%

Requirement for Foxd3 in the maintenance of neural crest progenitors

et al. 2008

View full text Add to dashboard Cite

Understanding the molecular mechanisms of stem cell maintenance is crucial for the ultimate goal of manipulating stem cells for the treatment of disease. Foxd3 is required early in mouse embryogenesis; Foxd3 -/-embryos fail around the time of implantation, cells of the inner cell mass cannot be maintained in vitro, and blastocyst-derived stem cell lines cannot be established. Here, we report that Foxd3 is required for maintenance of the multipotent mammalian neural crest. Using tissue-specific deletion of Foxd3 in the neural crest, we show that Foxd3 flox/-; Wnt1-Cre mice die perinatally with a catastrophic loss of neural crest-derived structures. Cranial neural crest tissues are either missing or severely reduced in size, the peripheral nervous system consists of reduced dorsal root ganglia and cranial nerves, and the entire gastrointestinal tract is devoid of neural crest derivatives. These results demonstrate a global role for this transcriptional repressor in all aspects of neural crest maintenance along the anterior-posterior axis, and establish an unprecedented molecular link between multiple divergent progenitor lineages of the mammalian embryo.

show abstract

Stem Cell Self-Renewal and Cancer Cell Proliferation Are Regulated by Common Networks That Balance the Activation of Proto-oncogenes and Tumor Suppressors

Cited by 126 publications

References 97 publications

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

Stem cell self-renewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis

Requirement for Foxd3 in the maintenance of neural crest progenitors

Contact Info

Product

Resources

About