scholarly journals Periostin Short Fragment with Exon 17 via Aberrant Alternative Splicing Is Required for Breast Cancer Growth and Metastasis

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 892
Author(s):  
Yuka Ikeda-Iwabu ◽  
Yoshiaki Taniyama ◽  
Naruto Katsuragi ◽  
Fumihiro Sanada ◽  
Nobutaka Koibuchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Matrix Protein ◽  
Interaction Analysis ◽  
Terminal Region ◽  
Cancer Growth ◽  
Collagen Gene ◽  
Short Fragment ◽  
Breast Cancer Growth

Background: Periostin (POSTN) is a 93 kDa matrix protein that helps to regulate collagen gene expression in the extracellular matrix. POSTN overexpression is a prognostic factor in malignant cancers; however, some researchers have observed it in the stroma, whereas others have reported it on tumors. Objective: This study aimed to investigate the function of POSTN on tumors. Methods and Results: We found that POSTN in cancer cells can be detected by using an antibody against the POSTN C-terminal region exon 17 (Ex17 antibody), but not with an antibody against the POSTN N-terminal region exon 12 (Ex12 antibody) in patients with breast cancer. In a fraction secreted from fibroblasts, LC–MS/MS analysis revealed a short fragment of POSTN of approximately 40 kDa with exon 17. In addition, molecular interaction analysis showed that POSTN with exon 17, but not POSTN without exon 17, bound specifically to wnt3a, and the Ex17 antibody inhibited the binding. Conclusion: A short fragment of POSTN with exon 17, which originates in the fibroblasts, is transported to cancer cells, whereas POSTN fragments without exon 17 are retained in the stroma. The Ex17 antibody inhibits the binding between POSTN exon 17 and wnt3a.

scholarly journals Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages

2016 ◽  
Vol 15 (8) ◽  
pp. 1931-1942 ◽  
Author(s):  
Stephen Iwanowycz ◽  
Junfeng Wang ◽  
Johnie Hodge ◽  
Yuzhen Wang ◽  
Fang Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Growth ◽  
Feedforward Loop ◽  
Breast Cancer Growth

scholarly journals L-Ascorbic Acid Inhibits Breast Cancer Growth by Inducing IRE/JNK/CHOP-Related Endoplasmic Reticulum Stress-Mediated p62/SQSTM1 Accumulation in the Nucleus

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1351 ◽  
Author(s):  
Youn Kyung Choi ◽  
Jung-Il Kang ◽  
Sanghoon Han ◽  
Young Ree Kim ◽  
Jaemin Jo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Ascorbic Acid ◽  
Er Stress ◽  
Cancer Cells ◽  
Cancer Growth ◽  
Autophagic Flux ◽  
Sequestosome 1 ◽  
Breast Cancer Growth

Anticancer effects of L-ascorbic acid (Vitamin C, L-AA) have been reported in various types of cancers. L-AA intake reduces breast cancer recurrence and mortality; however, the role of L-AA in the treatment of breast cancer remains poorly understood. In this study, we investigated the effect and mechanism action of L-AA on breast cancer growth. L-AA inhibited the growth of breast cancer cells by inducing apoptotic cell death at the evaluated treatment concentrations without affecting normal cells. Moreover, L-AA induces autophagosome formation via regulation of mammalian target of rapamycin (mTOR), Beclin1, and autophagy-related genes (ATGs) and increased autophagic flux. Notably, we observed that L-AA increased p62/SQSTM1 (sequestosome 1) protein levels. Accumulation of p62 protein in cancer cells in response to stress has been reported, but its role in cancer regulation remains controversial. Here, we demonstrated that L-AA-induced p62 accumulation is related to L-AA-induced breast cancer growth inhibition. Furthermore, L-AA induced endoplasmic reticulum (ER) stress via the IRE–JNK–CHOP (inositol-requiring endonuclease–c-Jun N-terminal kinase–C/EBP homologous protein) signaling pathways, which increased the nuclear levels of p62/SQSTM1. These findings provide evidence that L-AA-induced ER stress could be crucial for p62 accumulation-dependent cell death, and L-AA can be useful in breast cancer treatment.

scholarly journals Osteocytic Connexin Hemichannels Modulate Oxidative Bone Microenvironment and Breast Cancer Growth

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6343
Author(s):  
Yi Tian ◽  
Manuel A. Riquelme ◽  
Chao Tu ◽  
Yumeng Quan ◽  
Xiaowen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Gap Junctions ◽  
Cancer Cells ◽  
Connexin 43 ◽  
Breast Cancer Cells ◽  
Dominant Negative ◽  
Cancer Growth ◽  
Breast Cancer Growth

Osteocytes, the most abundant bone cell types embedded in the mineral matrix, express connexin 43 (Cx43) hemichannels that play important roles in bone remodeling and osteocyte survival. Estrogen deficiency decreases osteocytic Cx43 hemichannel activity and causes a loss in osteocytes’ resistance to oxidative stress (OS). In this study, we showed that OS reduced the growth of both human (MDA-MB-231) and murine (Py8119) breast cancer cells. However, co-culturing these cells with osteocytes reduced the inhibitory effect of OS on breast cancer cells, and this effect was ablated by the inhibition of Cx43 hemichannels. Py8119 cells were intratibially implanted in the bone marrow of ovariectomized (OVX) mice to determine the role of osteocytic Cx43 hemichannels in breast cancer bone metastasis in response to OS. Two transgenic mice overexpressing dominant-negative Cx43 mutants, R76W and Δ130-136, were adopted for this study; the former inhibits gap junctions while the latter inhibits gap junctions and hemichannels. Under normal conditions, Δ130-136 mice had significantly more tumor growth in bone than that in WT and R76W mice. OVX increased tumor growth in R76W but had no significant effect on WT mice. In contrast, OVX reduced tumor growth in Δ130-136 mice. To confirm the role of OS, WT and Δ130-136 mice were administered the antioxidant N-acetyl cysteine (NAC). NAC increased tumor burden and growth in Δ130-136 mice but not in WT mice. Together, the data suggest that osteocytes and Cx43 hemichannels play pivotal roles in modulating the oxidative microenvironment and breast cancer growth in the bone.

scholarly journals The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression

Oncotarget ◽  
2016 ◽  
Vol 7 (11) ◽  
pp. 13106-13121 ◽  
Author(s):  
Jonathan H. Shepherd ◽  
Ivan P. Uray ◽  
Abhijit Mazumdar ◽  
Anna Tsimelzon ◽  
Michelle Savage ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Cancer Growth ◽  
Basal Like Breast Cancer ◽  
Breast Cancer Growth

scholarly journals p42/p44 MAPK-mediated Stat3Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth

2013 ◽  
Vol 20 (2) ◽  
pp. 197-212 ◽  
Author(s):  
Mercedes Tkach ◽  
Cinthia Rosemblit ◽  
Martín A Rivas ◽  
Cecilia J Proietti ◽  
María Celeste Díaz Flaqué ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
Breast Cancer Cells ◽  
Receptor Expression ◽  
Cancer Growth ◽  
Stat3 Phosphorylation ◽  
Breast Cancer Growth

Stat3 is a signaling node for multiple oncogenic pathways and is therefore frequently active in breast cancer. As experimental and clinical evidence reveals that progestins are key players in controlling mammary gland tumorigenesis, we studied Stat3 participation in this event. We have previously shown that progestins induce Stat3Tyr705 phosphorylation and its transcriptional activation in breast cancer cells. In this study, we demonstrate that progestins also induce Stat3 phosphorylation at Ser727 residue, which occurs via activation of c-Src/p42/p44 MAPK pathways in murine progestin-dependent C4HD cells and in T-47D cells. Expression of a Stat3S727A vector, which carries a serine-to-alanine substitution at codon 727, shows that Stat3Ser727 phosphorylation is required for full transcriptional activation of cyclin D1 gene expression by progestins and for in vivo Stat3 recruitment on cyclin D1 promoter. Transfection of Stat3S727A in murine and human breast cancer cells abolished progestin-induced in vitro and in vivo growth. Moreover, we found a positive correlation between progesterone receptor expression and nuclear localization of Stat3Ser727 phosphorylation in breast cancer biopsies. These data highlight Stat3 phosphorylation in Ser727 residue as a nongenomic action by progestins, necessary to promote breast cancer growth.

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