Volume 52 Issue 1
Jan.  2021
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ZHOU Jing-feng, ZHOU Qin, CHEN Chun, et al. A Review of the Roles of Endoplasmic Reticulum Stress in Cancer Cell Metastasis[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 11-15. doi: 10.12182/20210160503
Citation: ZHOU Jing-feng, ZHOU Qin, CHEN Chun, et al. A Review of the Roles of Endoplasmic Reticulum Stress in Cancer Cell Metastasis[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 11-15. doi: 10.12182/20210160503

A Review of the Roles of Endoplasmic Reticulum Stress in Cancer Cell Metastasis

doi: 10.12182/20210160503
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  • Corresponding author: E-mail:panjx2@mail.sysu.edu.cn
  • Received Date: 2020-11-04
  • Rev Recd Date: 2020-12-28
  • Publish Date: 2021-01-20
  • Metastasis is a multistep and low-efficiency biological process driven by acquisition of genetic and/or epigenetic alterations within tumor cells. These evolutionary alterations enable tumor cells to thrive in the inhospitable microenvironment they encounter in the process of metastasis and eventually lead to macroscopic metastases in distant organs. The unfolded protein response (UPR) induced by endoplasmic reticulum (ER) stress is one of the most important mechanisms regulating cellular adaptation to an adverse microenvironment. UPR is involved in all stages of metastasis, playing an important role in tumor cell growth, survival, and differentiation and the process of maintaining protein hemostasis. Sustained activation of ER stress sensors endows tumor cells with better epithelial–mesenchymal transition (EMT), survival, immune escape, angiogenesis, cellular adhesion, dormancy-to reactivation capacity in the process of metastasis. Here, we discussed the role of UPR in regulating the above-mentioned abilities of tumor cells during metastasis, providing a reference for development of new targets for the treatment of tumor metastasis.UPR in regulating the above-mentioned characteristics and mechanisms of tumor cells during metastasis, providing a reference for development of new targets for the treatment of tumor metastasis.
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  • [1]
    RAYMUNDO D P, DOULTSINOS D, GUILLORY X, et al. Pharmacological targeting of IRE1 in cancer. Trends Cancer,2020,6(12): 1018–1030. doi: 10.1016/j.trecan.2020.07.006
    LIMIA C M, SAUZAY C, URRA H, et al. Emerging roles of the endoplasmic reticulum associated unfolded protein response in cancer cell migration and invasion. Cancers (Basel),2019,11(5): 631. doi: 10.3390/cancers11050631
    URRA H, DUFEY E, AVRIL T, et al. Endoplasmic reticulum stress and the hallmarks of cancer. Trends Cancer,2016,2(5): 252–262. doi: 10.1016/j.trecan.2016.03.007
    CRAENE B D, BERX G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer,2013,13(2): 97–110. doi: 10.1038/nrc3447
    OAKES S A. Endoplasmic reticulum stress signaling in cancer cells. Am J Pathol,2020,190(5): 934–946. doi: 10.1016/j.ajpath.2020.01.010
    VALASTYAN S, WEINBERG R A. Tumor metastasis: molecular insights and evolving paradigms. Cell,2011,147(2): 275–292. doi: 10.1016/j.cell.2011.09.024
    SENFT D, RONAI Z A. Adaptive stress responses during tumor metastasis and dormancy. Trends Cancer,2016,2(8): 429–442. doi: 10.1016/j.trecan.2016.06.004
    CHAFFER C L, WEINBERG R A. A perspective on cancer cell metastasis. Science,2011,331(6024): 1559–1564. doi: 10.1126/science.1203543
    MASSAGUÉ J, OBENAUF A C. Metastatic colonization by circulating tumour cells. Nature,2016,529(7586): 298–306. doi: 10.1038/nature17038
    HSU S K, CHIU C C, DAHMS H U, et al. Unfolded protein response (UPR) in survival, dormancy, immunosuppression, metastasis, and treatments of cancer cells. Int J Mol Sci,2019,20(10): 2518[2020-12-25]. https://doi.org/10.3390/ijms20102518. doi: 10.3390/ijms20102518
    BARTOSZEWSKA S, COLLAWN J F. Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia. Cell Mol Biol Lett,2020,25: 18[2020-12-25]. https://doi.org/10.1186/s11658-020-00212-1. doi: 10.1186/s11658-020-00212-1
    VANACKER H, VETTERS J, MOUDOMBI L, et al. Emerging role of the unfolded protein response in tumor immunosurveillance. Trends Cancer,2017,3(7): 491–505. doi: 10.1016/j.trecan.2017.05.005
    BRABLETZ T, KALLURI R, NIETO M A, et al. EMT in cancer. Nat Rev Cancer,2018,18(2): 128–134. doi: 10.1038/nrc.2017.118
    SANTAMARÍA P G, MAZÓN M J, ERASO P, et al. UPR: an upstream signal to EMT induction in cancer. J Clin Med,2019,8(5): 624[2020-12-25]. https://doi.org/10.3390/jcm8050624. doi: 10.3390/jcm8050624
    HAN C C, WAN F S. New insights into the role of endoplasmic reticulum stress in breast cancer metastasis. J Breast Cancer,2018,21(4): 354–362. doi: 10.4048/jbc.2018.21.e51
    LI H, CHEN X, GAO Y, et al. XBP1 induces snail expression to promote epithelial- to-mesenchymal transition and invasion of breast cancer cells. Cell Signal,2015,27(1): 82–89. doi: 10.1016/j.cellsig.2014.09.018
    CUEVAS E P, ERASO P, MAZÓN M J, et al. LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 signalling pathway. Sci Rep,2017,7: 44988[2020-12-25]. https://doi.org/10.1038/srep44988. doi: 10.1038/srep44988
    SHAH P P, DUPRE T V, SISKIND L J, et al. Common cytotoxic chemotherapeutics induce epithelial-mesenchymal transition (EMT) downstream of ER stress. Oncotarget,2017,8(14): 22625–22639.
    CUBILLOS-RUIZ J R, BETTIGOLE S E, GLIMCHER L H. Tumorigenic and immunosuppressive effects of endoplasmic reticulum stress in cancer. Cell,2017,168(4): 692–706. doi: 10.1016/j.cell.2016.12.004
    GRIVENNIKOV S I, KARIN M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev,2010,21(1): 11–19. doi: 10.1016/j.cytogfr.2009.11.005
    BI M, NACZKI C, KORITZINSKY M, et al. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. Embo J,2005,24(19): 3470–3481. doi: 10.1038/sj.emboj.7600777
    DEY S, SAYERS C M, VERGINADIS I I, et al. ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis. J Clin Invest,2015,125(7): 2592–2608. doi: 10.1172/JCI78031
    NAKATOGAWA H. Autophagic degradation of the endoplasmic reticulum. Proc Jpn Acad Ser B Phys Biol Sci,2020,96(1): 1–9. doi: 10.2183/pjab.96.001
    MOREL E. Endoplasmic reticulum membrane and contact site dynamics in autophagy regulation and stress response. Front Cell Dev Biol,2020,8: 343[2020-12-25]. https://doi.org/10.3389/fcell.2020.00343. doi: 10.3389/fcell.2020.00343
    HØYER-HANSEN M, JÄÄTTELÄ M. Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ,2007,14(9): 1576–1582. doi: 10.1038/sj.cdd.4402200
    BERNALES S, MCDONALD K L, WALTER P. Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biol, 2006, 4(12): e423[2020-12-25]. https://doi.org/10.1371/journal.pbio.0040423.
    B'CHIR W, MAURIN A C, CARRARO V, et al. The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res,2013,41(16): 7683–7699. doi: 10.1093/nar/gkt563
    CUBILLOS-RUIZ J R, BETTIGOLE S E, GLIMCHER L H. Molecular pathways: immunosuppressive roles of IRE1α-XBP1 signaling in dendritic cells of the tumor microenvironment. Clin Cancer Res,2016,22(9): 2121–2126. doi: 10.1158/1078-0432.CCR-15-1570
    SONG M, SANDOVAL T A, CHAE C S, et al. IRE1α-XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity. Nature,2018,562(7727): 423–428. doi: 10.1038/s41586-018-0597-x
    THEVENOT P T, SIERRA R A, RABER P L, et al. The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. Immunity,2014,41(3): 389–401. doi: 10.1016/j.immuni.2014.08.015
    AUF G, JABOUILLE A, GUÉRIT S, et al. Inositol-requiring enzyme 1α is a key regulator of angiogenesis and invasion in malignant glioma. Proc Natl Acad Sci U S A,2010,107(35): 15553–15558. doi: 10.1073/pnas.0914072107
    LIANG H, XIAO J, ZHOU Z, et al. Hypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis. Oncogene,2018,37(15): 1961–1975. doi: 10.1038/s41388-017-0089-8
    CHEN X, ILIOPOULOS D, ZHANG Q, et al. XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway. Nature,2014,508(7494): 103–107. doi: 10.1038/nature13119
    WANG Y, ALAM G N, NING Y, et al. The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway. Cancer Res,2012,72(20): 5396–5406. doi: 10.1158/0008-5472.CAN-12-0474
    CHO J, MIN H Y, PEI H, et al. The ATF6-EGF pathway mediates the awakening of slow-cycling chemoresistant cells and tumor recurrence by stimulating tumor angiogenesis. Cancers (Basel),2020,12(7): 1772[2020-12-25]. https://doi.org/10.3390/cancers12071772. doi: 10.3390/cancers12071772
    GHOSH R, LIPSON K L, SARGENT K E, et al. Transcriptional regulation of VEGF-A by the unfolded protein response pathway. PLoS One, 2010, 5(3): e9575[2020-12-25]. https://doi.org/10.1371/journal.pone.0009575.
    URRA H, HENRIQUEZ D R, CÁNOVAS J, et al. IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A. Nat Cell Biol,2018,20(8): 942–953. doi: 10.1038/s41556-018-0141-0
    YUAN X P, DONG M, LI X, et al. GRP78 promotes the invasion of pancreatic cancer cells by FAK and JNK. Mol Cell Biochem,2015,398(1/2): 55–62. doi: 10.1007/s11010-014-2204-2
    LU X, MU E, WEI Y, et al. VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. Cancer Cell,2011,20(6): 701–714. doi: 10.1016/j.ccr.2011.11.002
    XU L Y, ZHANG W J, ZHANG X H, et al. Endoplasmic reticulum stress in bone metastases. Front Oncol,2020,10: 1100[2020-12-25]. https://doi.org/10.3389/fonc.2020.01100. doi: 10.3389/fonc.2020.01100
    ROBINSON N J, PARKER K A, SCHIEMANN W P. Epigenetic plasticity in metastatic dormancy: mechanisms and therapeutic implications. Ann Transl Med,2020,8(14): 903[2020-12-25]. htttps://doi.org/10.21037/atm.2020.02.177. doi: 10.21037/atm.2020.02.177
    GIANCOTTI F G. Mechanisms governing metastatic dormancy and reactivation. Cell,2013,155(4): 750–764. doi: 10.1016/j.cell.2013.10.029
    FANG C, KANG Y B. Cellular plasticity in bone metastasis. Bone,2020: 115693[2020-12-25]. https://doi.org/10.1016/j.bone.2020.115693. doi: 10.1016/j.bone.2020.115693
    KORENTZELOS D, CLARK A M, WELLS A. A Perspective on therapeutic pan-resistance in metastatic cancer. Int J Mol Sci,2020,21(19): 7304[2020-12-25]. https://doi.org/10.3390/ijms21197304. doi: 10.3390/ijms21197304
    COLEMAN R E, CROUCHER P I, PADHANI A R, et al. Bone metastases. Nat Rev Dis Primers, 2020, 6(1): 83[2020-12-25]. https://doi.org/10.1038/s41572-020-00216-3.
    FARES J, FARES M Y, KHACHFE H H, et al. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther,2020,5(1): 28[2020-12-25]. https://doi.org/10.1038/s41392-020-0134-x. doi: 10.1038/s41392-020-0134-x
    RANGANATHAN A C, OJHA S, KOURTIDIS A, et al. Dual function of pancreatic endoplasmic reticulum kinase in tumor cell growth arrest and survival. Cancer Res,2008,68(9): 3260–3268. doi: 10.1158/0008-5472.CAN-07-6215
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