Phenotypic characterization of human colorectal cancer stem cells

Dalerba, Piero; Dylla, Scott J.; Park, In Kyung; Li, Rui; Wang, Xinhao; Cho, Robert W.; Hoey, Timothy; Gurney, Austin; Huang, Emina H.; Simeone, Diane M.; Shelton, Andrew; Parmiani, Giorgio; Castelli, Chiara; Clarke, Michael F.

doi:10.1073/pnas.0703478104

Cited by 1,934 publications

(1,672 citation statements)

References 32 publications

Supporting

Mentioning

1,571

Contrasting

Unclassified

Order By: Relevance

“…These results show that, in contrast to the anti‐proliferative effects of FUT9 activity in the bulk of colon cancer cells (Fig 3A–D), FUT9 activity may actually be required for the efficient expansion of TIC populations. This was further confirmed by flow cytometry analysis, showing that FUT9 silencing decreases the expression of a prominent colorectal cancer TIC marker CD44 (Dalerba et al , 2007; Qureshi‐Baig et al , 2017) in HCT116 cells (Fig 4C).…”

Section: Resultssupporting

confidence: 56%

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

Auslander

Cunningham

Toosi

et al. 2017

Molecular Systems Biology

View full text Add to dashboard Cite

Metabolic alterations play an important role in cancer and yet, few metabolic cancer driver genes are known. Here we perform a combined genomic and metabolic modeling analysis searching for metabolic drivers of colorectal cancer. Our analysis predicts FUT9, which catalyzes the biosynthesis of Ley glycolipids, as a driver of advanced‐stage colon cancer. Experimental testing reveals FUT9's complex dual role; while its knockdown enhances proliferation and migration in monolayers, it suppresses colon cancer cells expansion in tumorspheres and inhibits tumor development in a mouse xenograft models. These results suggest that FUT9's inhibition may attenuate tumor‐initiating cells (TICs) that are known to dominate tumorspheres and early tumor growth, but promote bulk tumor cells. In agreement, we find that FUT9 silencing decreases the expression of the colorectal cancer TIC marker CD44 and the level of the OCT4 transcription factor, which is known to support cancer stemness. Beyond its current application, this work presents a novel genomic and metabolic modeling computational approach that can facilitate the systematic discovery of metabolic driver genes in other types of cancer.

show abstract

Section: Resultssupporting

confidence: 56%

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

Auslander

Cunningham

Toosi

et al. 2017

Molecular Systems Biology

View full text Add to dashboard Cite

show abstract

“…Initially, it was believed that CSCs only comprise a small fraction in whole tumor cell populations, such as reported in solid and haematopoietic cancers (Al-Hajj et al, 2003;Jamieson et al, 2004;Singh et al, 2004;Dalerba et al, 2007;O/'Brien et al, 2007). Recent reports, based on transplantation of a broad spectrum of both primary and xenografted melanomas, contradict those conclusions (Quintana et al, 2008;Boiko et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

et al. 2011

View full text Add to dashboard Cite

Identification and characterization of cancer stem cells (CSCs) in gastric cancer are difficult owing to the lack of specific markers and consensus methods. In this study, we show that cells with the CD90 surface marker in gastric tumors could be enriched under non-adherent, serumfree and sphere-forming conditions. These CD90 þ cells possess a higher ability to initiate tumor in vivo and could re-establish the cellular hierarchy of tumors from singlecell implantation, demonstrating their self-renewal properties. Interestingly, higher proportion of CD90 þ cells correlates with higher in vivo tumorigenicity of gastric primary tumor models. In addition, it was found that ERBB2 was overexpressed in about 25% of the gastric primary tumor models, which correlates with the higher level of CD90 expression in these tumors. Trastuzumab (humanized anti-ERBB2 antibody) treatment of hightumorigenic gastric primary tumor models could reduce the CD90 þ population in tumor mass and suppress tumor growth when combined with traditional chemotherapy. Moreover, tumorigenicity of tumor cells could also be suppressed when trastuzumab treatment starts at the same time as cell implantation. Therefore, we have identified a CSC population in gastric primary tumors characterized by their CD90 phenotype. The finding that trastuzumab targets the CSC population in gastric tumors suggests that ERBB2 signaling has a role in maintaining CSC populations, thus contributing to carcinogenesis and tumor invasion. In conclusion, the results from this study provide new insights into the gastric tumorigenic process and offer potential implications for the development of anticancer drugs as well as therapeutic treatment of gastric cancers.

show abstract

“…Cancer cell heterogeneity and hierarchy may be resulted from both genetic and/or epigenetic causes. Increasing evidence from hematopoietic malignancies and solid tumors (including brain, breast, colorectal, head and neck cancers) has strongly supported the concept that a subpopulation of cancer cells in each tumor has greater potential of cancer initiation and repopulation (Lapidot et al, 1994;Bonnet and Dick, 1997;Al-Hajj et al, 2003;Hemmati et al, 2003;Singh et al, 2003;Galli et al, 2004;Singh et al, 2004;Ricci-Vitiani et al, 2007;O'Brien et al, 2007;Dalerba et al, 2007;Prince et al, 2007;Schatton et al, 2008). These cells were called cancer stem cells (CSCs) or tumor-initiating or propagating cells because they share some critical characteristics with normal stem cells, including the capacities for self-renewal, multi-lineage differentiation, and maintained proliferation (Reya et al, 2001;Vescovi et al, 2006;Bao et al, 2006a;Rosen and Jordan, 2009;Park and rich, 2009;Heddleston et al, 2010;Frank et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

et al. 2010

View full text Add to dashboard Cite

Glioblastomas (GBMs) are highly lethal primary brain tumors. Despite current therapeutic advances in other solid cancers, the treatment of these malignant gliomas remains essentially palliative. GBMs are extremely resistant to conventional radiation and chemotherapies. We and others have demonstrated that a highly tumorigenic subpopulation of cancer cells called GBM stem cells (GSCs) promotes therapeutic resistance. We also found that GSCs stimulate tumor angiogenesis by expressing elevated levels of VEGF and contribute to tumor growth, which has been translated into a useful therapeutic strategy in the treatment of recurrent or progressive GBMs. Furthermore, stem cell-like cancer cells (cancer stem cells) have been shown to promote metastasis. Although GBMs rarely metastasize beyond the central nervous system, these highly infiltrative cancers often invade into normal brain tissues preventing surgical resection, and GSCs display an aggressive invasive phenotype. These studies suggest that targeting GSCs may effectively reduce tumor recurrence and significantly improve GBM treatment. Recent studies indicate that cancer stem cells share core signaling pathways with normal somatic or embryonic stem cells, but also display critical distinctions that provide important clues into useful therapeutic targets. In this review, we summarize the current understanding and advances in glioma stem cell research, and discuss potential targeting strategies for future development of anti-GSC therapies.

show abstract

Phenotypic characterization of human colorectal cancer stem cells

Cited by 1,934 publications

References 32 publications

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

Contact Info

Product

Resources

About