Fra-2 overexpression upregulates pro-metastatic cell-adhesion molecules, promotes pulmonary metastasis, and reduces survival in a spontaneous xenograft model of human breast cancer

Abstract Purpose The transcription factor Fra-2 affects the invasive potential of breast cancer cells by dysregulating adhesion molecules in vitro. Previous results suggested that it upregulates the expression of E- and P-selectin ligands. Such selectin ligands are important members of the leukocyte adhesion cascade, which govern the adhesion and transmigration of cancer cells into the stroma of the host organ of metastasis. As so far, no in vivo data are available, this study was designed to elucidate the role of Fra-2 expression in a spontaneous breast cancer metastasis xenograft model. Methods The effect of Fra-2 overexpression in two stable Fra-2 overexpressing clones of the human breast cancer cell line MDA MB231 on survival and metastatic load was studied after subcutaneous injection into scid and E- and P-selectin-deficient scid mice. Results Fra-2 overexpression leads to a significantly shorter overall survival and a higher amount of spontaneous lung metastases not only in scid mice, but also in E- and P-deficient mice, indicating that it regulates not only selectin ligands, but also selectin-independent adhesion processes. Conclusion Thus, Fra-2 expression influences the metastatic potential of breast cancer cells by changing the expression of adhesion molecules, resulting in increased adherence to endothelial cells in a breast cancer xenograft model.

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Fra-2 Overexpression Upregulates Pro-metastatic Cell-adhesion Molecules, Promotes Pulmonary Metastasis and Reduces Survival in a Spontaneous Xenograft Model of Human Breast Cancer

10.21203/rs.3.rs-592522/v1 ◽

2021 ◽

Author(s):

Sabrina Arnold ◽

Jan Kortland ◽

Diana V. Maltseva ◽

Timur R. Samatov ◽

Susanne Lezius ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Adhesion Molecules ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

Lung Metastases ◽

Xenograft Model ◽

Human Breast ◽

Selectin Ligands

Abstract Purpose:The transcription factor Fra-2 affects the invasive potential of breast cancer cells by dysregulating adhesion molecules in vitro. Previous results suggested that it upregulates the expression of E- and P-selectin ligands. Such selectin ligands are important members of the leukocyte adhesion cascade, which govern the adhesion and transmigration of cancer cells into the stroma of the host organ of metastasis. As so far, no in vivo data are available, this study was designed to elucidate the role of Fra-2 expression in a spontaneous breast cancer metastasis xenograft model. Methods:The effect of Fra-2 overexpression in two stable Fra-2 overexpressing clones of the human breast cancer cell line MDA MB231 on survival and metastatic load was studied after subcutaneous injection into scid and E- and P-selectin deficient scid mice.Results:Fra-2 overexpression lead to a significantly shorter overall survival and a higher amount of spontaneous lung metastases not only in scid mice, but also in E- and P-deficient mice, indicating that it regulates not only selectin ligands, but also selectin-independent adhesion processes. Conclusion:Thus, Fra-2 expression influences the metastatic potential of breast cancer cells by changing the expression of adhesion molecules, resulting in increased adherence to endothelial cells in a breast cancer xenograft model.

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Association of human breast cancer CD44-/CD24- cells with delayed distant metastasis

eLife ◽

10.7554/elife.65418 ◽

2021 ◽

Vol 10 ◽

Author(s):

Xinbo Qiao ◽

Yixiao Zhang ◽

Lisha Sun ◽

Qingtian Ma ◽

Jie Yang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Distant Metastasis ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Human Breast ◽

Cell Conversion

Tumor metastasis remains the main cause of breast cancer-related deaths, especially delayed breast cancer distant metastasis. The current study assessed the frequency of CD44-/CD24- breast cancer cells in 576 tissue specimens for associations with clinicopathological features and metastasis and investigated the underlying molecular mechanisms. The results indicated that higher frequency (≥19.5%) of CD44-/CD24- cells was associated with delayed postoperative breast cancer metastasis. Furthermore, CD44-/CD24- triple negative breast cancer (TNBC) cells spontaneously converted into CD44+/CD24- cancer stem cells (CSCs) with properties similar to CD44+/CD24- CSCs from primary human breast cancer cells and parental TNBC cells in terms of stemness marker expression, self-renewal, differentiation, tumorigenicity and lung metastasis in vitro and in NOD/SCID mice. RNA sequencing identified several differentially expressed genes (DEGs) in newly converted CSCs and RHBDL2, one of the DEGs, expression was up-regulated. More importantly, RHBDL2 silencing inhibited the YAP1/USP31/NF-κB signaling and attenuated spontaneous CD44-/CD24- cell conversion into CSCs and their mammosphere formation. These findings suggest that the frequency of CD44-/CD24- tumor cells and RHBDL2 may be valuable for prognosis of delayed breast cancer metastasis, particularly for TNBC.

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MHP-1 inhibits cancer metastasis and restores topotecan sensitivity via regulating epithelial-mesenchymal transition and TGF-β signaling in human breast cancer cells

Phytomedicine ◽

10.1016/j.phymed.2016.06.013 ◽

2016 ◽

Vol 23 (10) ◽

pp. 1053-1063 ◽

Cited By ~ 9

Author(s):

Sensen Lin ◽

Xiaodan Lyu ◽

Jun Yu ◽

Li Sun ◽

Danyu Du ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mesenchymal Transition

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Abstract 5261: Novel resveratrol analogue, HS-1793, inhibits hypoxia-induced HIF-1 and VEGF expressions and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model

10.1158/1538-7445.am2016-5261 ◽

2016 ◽

Author(s):

Dong Hwan Kim ◽

Min Jeong Kim ◽

Bokyung Sung ◽

Yong Jung Kang ◽

Seong Yeon Hwang ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Xenograft Model ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mouse Xenograft ◽

Mouse Xenograft Model

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HS-1793, a resveratrol analogue, downregulates the expression of hypoxia-induced HIF-1 and VEGF and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model

International Journal of Oncology ◽

10.3892/ijo.2017.4058 ◽

2017 ◽

Vol 51 (2) ◽

pp. 715-723 ◽

Cited By ~ 11

Author(s):

Dong Hwan Kim ◽

Bokyung Sung ◽

Jin-Ah Kim ◽

Yong Jung Kang ◽

Seong Yeon Hwang ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Xenograft Model ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mouse Xenograft ◽

Mouse Xenograft Model

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Global Alternative Splicing Defects in Human Breast Cancer Cells

Cancers ◽

10.3390/cancers13123071 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3071

Author(s):

Jagyeong Oh ◽

Davide Pradella ◽

Yoonseong Kim ◽

Changwei Shao ◽

Hairi Li ◽

...

Keyword(s):

Breast Cancer ◽

Alternative Splicing ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

The Cancer Genome Atlas ◽

Cancer Type ◽

Human Breast ◽

Intrinsically Disordered

Breast cancer is the most frequently occurred cancer type and the second cause of death in women worldwide. Alternative splicing (AS) is the process that generates more than one mRNA isoform from a single gene, and it plays a major role in expanding the human protein diversity. Aberrant AS contributes to breast cancer metastasis and resistance to chemotherapeutic interventions. Therefore, identifying cancer-specific isoforms is the prerequisite for therapeutic interventions intended to correct aberrantly expressed AS events. Here, we performed RNA-mediated oligonucleotide annealing, selection, and ligation coupled with next-generation sequencing (RASL-seq) in breast cancer cells, to identify global breast cancer-specific AS defects. By RT-PCR validation, we demonstrate the high accuracy of RASL-seq results. In addition, we analyzed identified AS events using the Cancer Genome Atlas (TCGA) database in a large number of non-pathological and breast tumor specimens and validated them in normal and breast cancer samples. Interestingly, aberrantly regulated AS cassette exons in cancer tissues do not encode for known functional domains but instead encode for amino acids constituting regions of intrinsically disordered protein portions characterized by high flexibility and prone to be subjected to post-translational modifications. Collectively, our results reveal novel AS errors occurring in human breast cancer, potentially affecting breast cancer-related biological processes.

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Tanshinone I suppresses growth and invasion of human breast cancer cells, MDA-MB-231, through regulation of adhesion molecules

Carcinogenesis ◽

10.1093/carcin/bgn151 ◽

2008 ◽

Vol 29 (10) ◽

pp. 1885-1892 ◽

Cited By ~ 69

Author(s):

I. T. Nizamutdinova ◽

G. W. Lee ◽

J. S. Lee ◽

M. K. Cho ◽

K. H. Son ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Adhesion Molecules ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Tanshinone I

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DCLK1 Plays a Metastatic-Promoting Role in Human Breast Cancer Cells

BioMed Research International ◽

10.1155/2019/1061979 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Heshu Liu ◽

Tao Wen ◽

Ying Zhou ◽

Xiaona Fan ◽

Tan Du ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cell Line ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

Cancer Cell Line ◽

Breast Cancer Metastasis ◽

Human Breast Cancer Cells ◽

Human Breast

Background. Doublecortin-like kinase 1 (DCLK1) has been universally identified as a cancer stem cell (CSC) marker and is found to be overexpressed in many types of cancers including breast cancer. However, there is little data regarding the functional role of DCLK1 in breast cancer metastasis. In the present study, we sought to investigate whether and how DCLK1 plays a metastatic-promoting role in human breast cancer cells.Methods. We used Crispr/Cas9 technology to knock out DCLK1 in breast cancer cell line BT474, which basically possesses DCLK1 at a higher level, and stably overexpressed DCLK1 in another breast cancer cell line, T47D, that basically expresses DCLK1 at a lower level. We further analyzed the alterations of metastatic characteristics and the underlying mechanisms in these cells.Results. It was shown that, compared with the corresponding control cells, DCLK1 overexpression led to an increase in metastatic behaviors including enhanced migration and invasion of T47D cells. By contrast, forced depletion of DCLK1 drastically inhibited these metastatic characteristics in BT474 cells. Mechanistically, the epithelial-mesenchymal transition (EMT) program, which is critical for cancer metastasis, was prominently activated in DCLK1-overexpressing cancer cells, evidenced by a decrease in an epithelial marker ZO-1 and an enhancement in several mesenchymal markers including ZEB1 and Vimentin. In addition, DCLK1 overexpression induced the ERK MAPK pathway, which resultantly enhanced the expression of MT1-MMP that is also involved in cancer metastasis. Knockout of DCLK1 could reverse these events, further supporting a metastatic-promoting role for DCLK1.Conclusions. Collectively, our data suggested that DCLK1 overexpression may be responsible for the increased metastatic features in breast cancer cells. Targeting DCLK1 may become a therapeutic option for breast cancer metastasis.

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