Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells

Zhang, Yimin; Liao, Shichong; Fan, Wei; Wen, Wei; Wang, Changhua; Sun, Shengrong

doi:10.3892/or.2014.3479

Cited by 18 publications

(11 citation statements)

References 24 publications

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“…In contrast, CCL5 function in low-grade gliomas has not been explored, and the impact of CCL5 function on glioma biology remains unclear. Whereas little is known about CCL5 in brain tumors, increased CCL5 expression has been reported in lung, prostate, melanoma, colorectal, and breast cancer [67] , [85] , [86] , [87] , [88] , where a positive correlation between increased CCL5 expression and disease progression was identified [89] , [90] . In addition, CCL5-expressing melanoma cells form increasingly aggressive tumors in a concentration-dependent fashion [91] , and Ccl5 increases the growth of breast cancer cells in vitro [92] .…”

Section: Resultsmentioning

confidence: 99%

RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth

et al. 2015

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Solid cancers develop within a supportive microenvironment that promotes tumor formation and growth through the elaboration of mitogens and chemokines. Within these tumors, monocytes (macrophages and microglia) represent rich sources of these stromal factors. Leveraging a genetically engineered mouse model of neurofibromatosis type 1 (NF1) low-grade brain tumor (optic glioma), we have previously demonstrated that microglia are essential for glioma formation and maintenance. To identify potential tumor-associated microglial factors that support glioma growth (gliomagens), we initiated a comprehensive large-scale discovery effort using optimized RNA-sequencing methods focused specifically on glioma-associated microglia. Candidate microglial gliomagens were prioritized to identify potential secreted or membrane-bound proteins, which were next validated by quantitative real-time polymerase chain reaction as well as by RNA fluorescence in situ hybridization following minocycline-mediated microglial inactivation in vivo. Using these selection criteria, chemokine (C-C motif) ligand 5 (Ccl5) was identified as a chemokine highly expressed in genetically engineered Nf1 mouse optic gliomas relative to nonneoplastic optic nerves. As a candidate gliomagen, recombinant Ccl5 increased Nf1-deficient optic nerve astrocyte growth in vitro. Importantly, consistent with its critical role in maintaining tumor growth, treatment with Ccl5 neutralizing antibodies reduced Nf1 mouse optic glioma growth and improved retinal dysfunction in vivo. Collectively, these findings establish Ccl5 as an important microglial growth factor for low-grade glioma maintenance relevant to the development of future stroma-targeted brain tumor therapies.

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Section: Resultsmentioning

confidence: 99%

RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth

et al. 2015

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“…Tunicamycin, a pharmacological ER stress inducer, can stimulate tumor cell apoptosis [ 17 , 18 ]. Therefore, it has been used to develop an anti-cancer drug [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Inducer Tunicamycin Alters Hepatic Energy Homeostasis in Mice

Feng

Huang

Jiang

et al. 2017

IJMS

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Disorders of hepatic energy metabolism, which can be regulated by endoplasmic reticulum (ER) stress, lead to metabolic diseases such as hepatic steatosis and hypoglycemia. Tunicamycin, a pharmacological ER stress inducer, is used to develop an anti-cancer drug. However, the effects of tunicamycin on hepatic energy metabolism have not been well elucidated. Mice were intraperitoneally injected with tunicamycin or vehicle. Twenty-four hours later, hepatic triglyceride and glycogen content and serum lipids profiles were analyzed, as well as the expression of lipogenic and gluconeogenic genes. Tunicamycin significantly induced hepatic a yellowish color and ER stress, as well as increasing serum levels of aspartate transaminase and alanine transaminase. Besides, tunicamycin remarkably increased hepatic triglyceride content and suppressed the expression of apolipoprotein B100. In addition, tunicamycin-treated mice had lower serum levels of triglyceride, apolipoprotein B, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Gene expression of peroxisome proliferator-activated receptor α was decreased by tunicamycin, but the protein level was increased. Furthermore, blood glucose level and hepatic glycogen content were decreased in tunicamycin-treated mice. Protein kinase B signaling was attenuated in the tunicamycin-treated liver, but the expression and activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were unchanged. Tunicamycin alters hepatic energy homeostasis by increasing triglyceride accumulation and decreasing glycogen content.

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“…Research has also shown that U-STAT3 can effectively compete with non-phosphorylated inhibitory κB (IκB) in binding with nuclear factor (NF)-κB to form a new transcription factor. The new transcription factor could induce the expression of CCL5 (Yang et al, 2005;Yang and Stark, 2008;Zhang et al, 2014). Therefore, we detect the expressions of phosphorylated STAT3, U-STAT3, and CCL5 in both MCF-7 cells and MCF-7/PTP1B shRNA cells by Western blot.…”

Section: Effect Of Ptp1b On the Production Of Ccl5mentioning

confidence: 99%

Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer

Liao

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:The protein tyrosine phosphatase 1B (PTP1B) is an important regulator of metabolism. The relationship between PTP1B and tumors is quite complex. The purpose of this study is to explore the expression pattern and role of PTP1B in breast cancer. The expression of PTP1B was detected in 67 samples of breast cancer tissue by Western blot. Cell growth assay, Transwell migration assay, and Scratch motility assay were used to examine the proliferation and migration of MCF-7 with and without PTP1B. The total levels and phosphorylated levels of signal transduction and activator of transcription 3 (STAT3) and the expression of C-C motif chemokine ligand 5 (CCL5) were also examined by Western blot. PTP1B was overexpressed in over 70% of breast cancer tissues, correlating with patients with estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-positive tumors. The data also showed that both tumor size and lymph node metastasis were significantly higher in patients with a higher level of PTP1B. The proliferation and migration of MCF-7 cells were found to be inhibited after knocking down the gene of PTP1B. Our data also showed that PTP1B could up-regulate the dephosphorylated level of STAT3, which could increase the expression of CCL5. These phenomena indicated that PTP1B may play a crucial role in the development of breast cancer.

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Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells

Cited by 18 publications

References 24 publications

RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth

RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth

Endoplasmic Reticulum Stress Inducer Tunicamycin Alters Hepatic Energy Homeostasis in Mice

Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer

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