The role of a new CD44st in increasing the invasion capability of the human breast cancer cell line MCF-7

Fang, Xin Jian; Jiang, Hua; Zhao, Xv Peng; Jiang, Wei

doi:10.1186/1471-2407-11-290

Cited by 27 publications

(25 citation statements)

References 28 publications

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“…21,22 CD44 and its variants can induce chemoresistance and invasion of human BC cell lines via different mechanisms. [23][24][25][26][27] Despite knowing the role that CD44 -HA plays in promoting BC invasion and metastasis, the underlying downstream signaling mechanism is nascent. In an attempt to elucidate these downstream signaling mechanisms, we generated a tetracycline (tet)-off-inducible system of CD44 expression both in vitro 14 and in vivo.…”

mentioning

confidence: 99%

Survivin Is a Novel Target of CD44-Promoted Breast Tumor Invasion

Abdraboh

Gaur

Hollenbach

et al. 2011

The American Journal of Pathology

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The hyaluronan (HA) receptor CD44 plays an essential role in cell-cell or cell-extracellular matrix communications and is a bioactive signal transmitter. Although a number of studies have described the function of CD44 in breast cancer (BC) metastasis, the underlying mechanisms have yet to be determined. By using a validated tetracycline-off-regulated CD44 expression system in the MCF-7 cell line combined with microarray analysis, we identified survivin (SVV) as a potential downstream transcriptional target of CD44. To test the hypothesis that SVV underpins CD44-promoted BC cell invasion, we combined molecular and pharmacologic approaches and showed that CD44 induction increased SVV expression levels, which in turn promotes BC cell invasion. Further, clinical analysis of breast tissue samples showed that SVV expression patterns paralleled those of the standard form of CD44 during breast tumor progression. More interestingly, we identified the PI3K/E2F1 pathway as a potential molecular link between HA/CD44 activation and SVV transcription. In addition to identifying SVV as a target for HA/CD44 signaling, this investigation provides a better understanding of the molecular mechanisms that underpin the novel function of SVV in breast cancer metastasis. Breast cancer (BC) is the most common cancer and the second most common cause of cancer-related deaths in women in the United States, with more than 175,000 women being diagnosed annually. 1,2 In the later stages of progression, BC cells metastasize from the original tumor site and travel through the vasculature to distant organs such as liver, lungs, brain, and bone. [2][3][4][5] Although the involvement of cell adhesion molecules in cancer development, progression, and metastasis has been established and discussed extensively in the literature, the mechanisms underlying their implication is still nascent. 6 -9 The hyaluronan (HA) receptor CD44, a multistructural and multifunctional cell adhesion molecule involved in cell-cell and cell-extracellular matrix interactions, functions as a bioactive signaling transmitter involved in a variety of cellular responses, including lymphocyte homing, hematopoiesis, inflammation, tumorigenesis, angiogenesis, and metastasis. 10 -13 The CD44 -HA complex initiates a series of intracellular signaling events that lead to migration, adhesion, invasion, proliferation, and differentiation of a variety of cells. The transduction of HA/CD44 signaling can occur through various mechanisms including the following: i) HA binding to CD44 can initiate the extracellular clustering of CD44, resulting in the activation of downstream kinases, 14 ii) CD44 can serve as a co-receptor physically associated with other cell signaling receptors, [15][16][17][18] iii) CD44 can serve as a docking protein for pericellular or cytoplasmic proteins, 19,20 and iv) the transmembrane domain of CD44 can be cleaved, allowing the translocation of the cytoplasmic domain to the nucleus, where it functions as a transcription factor regulating the expression of target gen...

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mentioning

confidence: 99%

Survivin Is a Novel Target of CD44-Promoted Breast Tumor Invasion

Abdraboh

Gaur

Hollenbach

et al. 2011

The American Journal of Pathology

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“…miR-21) has been shown to increase the invasiveness of normal and cancer cells (56,57). In some instances non-invasive cells can be transformed into invasive cells, whereas in other cases the invasiveness of a cell can be increased due to changes in the expression levels of specific miRNAs (or genes) (58,59). Although our study demonstrates no effect of miR-9 overexpression on the invasiveness of the non-invasive MCF-7 cell line, the overexpression of miR-9 elicited a significant reduction in the invasiveness of the highly invasive MDA-MB-231 cell line.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-9 Inhibition of Cell Proliferation and Identification of Novel miR-9 Targets by Transcriptome Profiling in Breast Cancer Cells

Selcuklu

Donoghue

Rehmet

et al. 2012

Journal of Biological Chemistry

171

143

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Background: Dysregulation of miRNAs is associated with breast cancer. Results: MiR-9 overexpression and transcriptome analysis reveals novel miR-9 targets, including MTHFD2, which can recapitulate anti-proliferative effects of miR-9 overexpression. Conclusion: MiR-9 displays tumor suppressor-like activity in breast cancer cells; MTHFD2 contributes to this activity. Significance: Understanding miR-9-directed regulation of the breast cancer transcriptome is important for diagnosis and therapeutics.

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“…The human breast cancer MCF-7 cell line and the doxorubicin-resistant human breast cancer MCF-7/Adr cell line were purchased from the Cell Bank of the Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China). MCF-7 cells were cultured as described previously (2). Cells were maintained in RPMI-1640 medium (Invitrogen, Carlsbad, CA, USA) containing 10% fetal bovine serum (FBS; Hangzhou Sijiqing Biological Engineering Materials Co., Ltd., Hangzhou, China) at 37˚C in a humidified atmosphere containing 5% CO 2 , while MCF-7/Adr cells were maintained in a medium containing 0.2 µg/ml doxorubicin, with drug withdrawal occurring 1 week prior to the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous study, the multidrugresistant human breast cancer MCF-7/Adr cells were used to clone the short-tail isoform of CD44 (CD44st), a novel shorttail isoform of CD44, which contains exons 1-4 and 16-17, and 1-205 base pairs of exon 18. The CD44 family members and their structures have been described previously (2).…”

Section: Introductionmentioning

confidence: 99%

“…It has been found that both CD44st mRNA and CD44st protein are highly expressed in multidrug-resistant MCF-7/Adr, Lovo/Adr, K562/Adr and HL-60/Adr cell lines, (2,10,11). To investigate the role of the transcription factor NF-κB in doxorubicin-induced drug resistance and the association with CD44st expression, we used low-dose doxorubicin to induce MDR in human breast cancer MCF-7 cells and determined the expression of MDR1, CD44st and NF-κB mRNA in these multidrug-resistant MCF-7 cells.…”

Section: Introductionmentioning

confidence: 99%

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Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells

et al. 2014

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Abstract. CD44, a major receptor for hyaluronan (HA), is a member of a class of adhesion molecules of unknown classification involved in cell proliferation, differentiation, migration, angiogenesis, and the presentation of specific cytokines to the corresponding receptors as well as in cell signaling transduction. It has recently been discovered that CD44, a marker of tumor stem cells, is involved in the drug resistance and invasion of multiple types of tumors. The 20 exons in the CD44 gene that are alternatively spliced, give rise to many CD44 isoforms, possibly including tumor-specific sequences. Dozens of CD44 isoforms have been found, to date, and the standard CD44 (CD44s) isoform is the most common. We recently showed that a novel short-tail isoform of CD44 (CD44st) was expressed in multidrug-resistant human breast cancer MCF-7/Adr cells. Moreover, the novel CD44st was able to interact with HA and regulate the expression of matrix metalloproteinase (MMP)-2 and MMP-9, which increased the invasive capability of MCF-7 cells through the Ras/MAPK signaling pathway. In the present study, we verified that MCF-7 cells subjected to drug pressure develop multidrug resistance to doxorubicin, and the expression levels of multidrug resistance protein 1 (MDR1), CD44st and nuclear factor-κB (NF-κB) mRNA and protein were gradually upregulated in a dose-dependent manner in MCF-7 cells treated with doxorubicin. HA increases the secretion of MMP-2 and MMP-9 in multidrug-resistant MCF-7 cells and affected the invasive ability of MCF-7 cells through the upregulation of CD44st expression, and such an effect was blocked by the NF-κB-specific inhibitor BMS-345541.

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The role of a new CD44st in increasing the invasion capability of the human breast cancer cell line MCF-7

Cited by 27 publications

References 28 publications

Survivin Is a Novel Target of CD44-Promoted Breast Tumor Invasion

Survivin Is a Novel Target of CD44-Promoted Breast Tumor Invasion

MicroRNA-9 Inhibition of Cell Proliferation and Identification of Novel miR-9 Targets by Transcriptome Profiling in Breast Cancer Cells

Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells

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