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Article

Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis

  • Authors:
    • Fen Yang
    • Xiao Yan Tang
    • Hao Liu
    • Zhi Wen Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Tumor Radiotherapy, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China, Department of Clinical Laboratory, Nanjing Chest Hospital, Nanjing, Jiangsu, P.R. China, Department of Pharmacy, Bengbu Medical College, Bengbu, Anhui, P.R. China
  • Pages: 2113-2120
    |
    Published online on: January 20, 2016
       https://doi.org/10.3892/or.2016.4580
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Abstract

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) induces ER stress which is observed in many human diseases, including breast cancer. Cellular adaptation to ER stress is mediated by the unfolded protein response (UPR), which aims at restoring ER homeostasis. Higher levels of GRP78 expression indicates constitutive activation of the UPR in breast cancer leading to breast cancer cells that are relatively resistant to ER stress-induced apoptosis. Tunicamycin (TM), an ER stress inducer, constitutively activates the mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK), and (MEK)/ERK pathway which plays a role in upregulation of GRP78 by ER stress in that inhibition of MEK by U0126 reduces the levels of GRP78 and blocks its upregulation by TM. Inhibition of the MEK/ERK pathway by U0126 sensitizes breast cancer cells to TM-induced apoptosis. Inhibition of GRP78 by siRNA knockdown enhances TM- and U0126-induced apoptosis in breast cancer cells. This sensitization of breast cancer cells to TM-induced apoptosis by inhibition of MEK/ERK and GRP78 is caspase-dependent, at least in part, by activation of caspase-4. These results seem to indicate that GRP78 has potential as a chemotherapeutical target and have important implications for new treatment strategies in breast cancer by combination with agents that induce ER stress with inhibitors of the MEK/ERK pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Yang F, Tang XY, Liu H and Jiang ZW: Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis. Oncol Rep 35: 2113-2120, 2016.
APA
Yang, F., Tang, X.Y., Liu, H., & Jiang, Z.W. (2016). Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis. Oncology Reports, 35, 2113-2120. https://doi.org/10.3892/or.2016.4580
MLA
Yang, F., Tang, X. Y., Liu, H., Jiang, Z. W."Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis". Oncology Reports 35.4 (2016): 2113-2120.
Chicago
Yang, F., Tang, X. Y., Liu, H., Jiang, Z. W."Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis". Oncology Reports 35, no. 4 (2016): 2113-2120. https://doi.org/10.3892/or.2016.4580
Copy and paste a formatted citation
x
Spandidos Publications style
Yang F, Tang XY, Liu H and Jiang ZW: Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis. Oncol Rep 35: 2113-2120, 2016.
APA
Yang, F., Tang, X.Y., Liu, H., & Jiang, Z.W. (2016). Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis. Oncology Reports, 35, 2113-2120. https://doi.org/10.3892/or.2016.4580
MLA
Yang, F., Tang, X. Y., Liu, H., Jiang, Z. W."Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis". Oncology Reports 35.4 (2016): 2113-2120.
Chicago
Yang, F., Tang, X. Y., Liu, H., Jiang, Z. W."Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis". Oncology Reports 35, no. 4 (2016): 2113-2120. https://doi.org/10.3892/or.2016.4580
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