CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3

Chun, Sang-Young; Chen, F; Washburn, Joseph; MacDonald, James W.; Innes, K L; Zhao, Ruihua; Cruz‐Correa, Marcia; Dang, Long H.; Dang, Duyen T.

doi:10.1038/sj.onc.1210258

Cited by 21 publications

(19 citation statements)

References 19 publications

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“…Our results are consistent with previous published data for metastasis models of other tissues: in a prostate cancer model, using the transgenic PB-HiMyc mice crossed with an IGFBP-3 knockout mouse model [28] showed that the absence of IGFBP-3 increased metastasis to distant organs. In other in vitro models, IG-FBP-3 inhibited migration of endometrial cancer cells [32] and was involved in inhibiting anchorage-independent growth [33], which could favor a metastatic process.…”

Section: Resultsmentioning

confidence: 99%

Germ line knockout of IGFBP-3 reveals influences of the gene on mammary gland neoplasia

Blouin

Bazile

Birman

et al. 2015

Breast Cancer Res Treat

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Insulin-like growth factor binding protein-3 (IGFBP-3) is an important carrier protein for insulin-like growth factors (IGFs) in the circulation. IGFBP-3 antagonizes the growth-promoting and anti-apoptotic activities of IGFs in experimental systems, but in certain contexts can increase IGF bioactivity, probably by increasing its half-life. The goal of this study was to investigate the role of IGFBP-3 in breast carcinogenesis and breast cancer metastasis. In the first part of the study, we exposed IGFBP-3 knockout and wild-type female mice to dimethylbenz[a]anthracene (DMBA) and followed them for appearance of primary tumors for up to 13 months. In the second part, mice of each genotype received an IV injection of 4T1 mammary carcinoma cells and then lung nodules were counted. Our results show that IGFBP-3 knockout mice developed breast tumors significantly earlier than the wild-type (13.9 ± 1.1 versus 22.5 ± 3.3 weeks, respectively, P = 0.0144), suggesting tumor suppression activity of IGFBP-3. In tumors of IGFBP-3 knockout mice, levels of phospho-AKT(Ser473) were increased compared to wild-type mice. The lung metastasis assay showed significantly more and larger lung nodules in IGFBP-3 knockout mice than in wild-type mice. While we observed increased levels of IGFBP-5 protein in the IGFBP-3 knockout mice, our findings suggest that this was not sufficient to completely compensate for the absence of IGFBP-3. Even though knockout of IGFBP-3 is associated with only a subtle phenotype under control conditions, our results reveal that loss of this gene has measurable effects on breast carcinogenesis and breast cancer metastasis.

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Section: Resultsmentioning

confidence: 99%

Germ line knockout of IGFBP-3 reveals influences of the gene on mammary gland neoplasia

Blouin

Bazile

Birman

et al. 2015

Breast Cancer Res Treat

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“…The role of CDX2 is probably also ambiguous in this matter, and may differ according to conditions. Two cancer cell line studies indicate that CDX2 under anchorage-independent growth conditions (resembling spreading cells) promotes proliferation and increases resistance to programmed cell death [94,95].…”

Section: Discussionmentioning

confidence: 99%

The clinical perspectives of CDX2 expression in colorectal cancer: A qualitative systematic review

et al. 2014

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“…CDX2, a Drosophila caudal-related homeobox transcription factor has been reported to promote tumorigenicity in a subset of human colorectal cancer cell lines (155). CDX2 also negatively regulates IGFBP-3 by specifically binding to the IGFBP-3 gene promoter and repressing IGFBP-3 transcription, protein expression, and secretion (155).…”

Section: Factors That Influence the Suppression Ormentioning

confidence: 99%

Unraveling Insulin-Like Growth Factor Binding Protein-3 Actions in Human Disease

2009

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The IGF system plays critical roles in somatic growth in an endocrine fashion (somatomedin hypothesis) as well as proliferation and differentiation of normal and malignant cells in a paracrine/autocrine fashion. IGFBP-3 is known to modulate the actions of IGFs in circulation as well as the immediate extracellular environment. Interestingly, apart from the ability to inhibit or enhance IGF actions, IGFBP-3 also exhibits very clear, distinct biological effects independent of the IGF/IGF-I receptor axis. Over the past decade it has become widely appreciated that IGF/IGF-IR-independent actions of IGFBP-3 (antiproliferative and proapoptotic effects) contribute to improving the pathophysiology of a variety of human diseases, such as cancer, diabetes, and malnutrition. Recent studies have implicated interaction of IGFBP-3 with a variety of proteins or signaling cascades critical to cell cycle control and apoptosis; however, the actual mechanism of IGFBP-3 action is still unclear. This review reinforces the concept in support of the IGF/IGF-IR axis-independent actions of IGFBP-3 and delineates potential underlying mechanisms involved and subsequent biological significance, focusing in particular on functional binding partners and the clinical significance of IGFBP-3 in the assessment of cancer risk.

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CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3

Cited by 21 publications

References 19 publications

Germ line knockout of IGFBP-3 reveals influences of the gene on mammary gland neoplasia

Germ line knockout of IGFBP-3 reveals influences of the gene on mammary gland neoplasia

The clinical perspectives of CDX2 expression in colorectal cancer: A qualitative systematic review

Unraveling Insulin-Like Growth Factor Binding Protein-3 Actions in Human Disease

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