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Direct reprogramming of stem cell properties in colon cancer cells by CD44.

ABSTRACT: Cancer progression is commonly segregated into processes of primary tumour growth and secondary metastasis. Recent evidence suggests that a subpopulation of cancer cells, cancer stem cells (CSCs), is responsible for tumour growth in cancer. However, the role of CSCs in cancer metastasis is unclear. In this study, we found that the C terminus of CD44 contributes to sphere formation and survival in vitro via the CD44-SRC-integrin axis. In addition, nuclear CD44/acetylated-STAT3 is required for clonal formation in vitro and tumourigenicity in vivo. Nuclear CD44 binds to various promoters identified by chromatin immunoprecipitation-seq, including that of c-myc and Twist1, leading to cell fate change through transcriptional reprogramming. We propose that nuclear CD44/acetylated-STAT3 performs an unexpected tumour-progressing function by enhancing cell outgrowth into structures where cells with properties of CSCs can be generated from differentiated somatic cells in suspension culture, and then exhibit attributes of cells that have undergone an epithelial-mesenchymal transition, leading to tumour metastasis, and a resulting worse prognosis.

SUBMITTER: Su YJ

PROVIDER: S-EPMC3160185 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Direct reprogramming of stem cell properties in colon cancer cells by CD44.

Su Ying-Jhen YJ Lai Hsin-Mei HM Chang Yi-Wen YW Chen Guan-Ying GY Lee Jia-Lin JL

The EMBO journal 20110624 15

Cancer progression is commonly segregated into processes of primary tumour growth and secondary metastasis. Recent evidence suggests that a subpopulation of cancer cells, cancer stem cells (CSCs), is responsible for tumour growth in cancer. However, the role of CSCs in cancer metastasis is unclear. In this study, we found that the C terminus of CD44 contributes to sphere formation and survival in vitro via the CD44-SRC-integrin axis. In addition, nuclear CD44/acetylated-STAT3 is required for clo ...[more]

PMID: 21701559

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Project description:The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential.The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44(+) cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44(+) cells consisted of mixed CD44(+) and CD44(-) cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44(+) and CD44(+) cells derived from CD44(+)-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44(-) cells. Furthermore, freshly sorted CD44(+) cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44(-) cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas.Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify the role of CD44 in tumor cell renewal and cancer propagation in the in vivo environment.

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Direct reprogramming of stem cell properties in colon cancer cells by CD44.

Publications

Direct reprogramming of stem cell properties in colon cancer cells by CD44.

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