bims-unfpre Biomed News
on Unfolded protein response
Issue of 2019‒05‒12
four papers selected by
Susan Logue
University of Manitoba


  1. Cancers (Basel). 2019 May 06. pii: E631. [Epub ahead of print]11(5):
    Limia CM, Sauzay C, Urra H, Hetz C, Chevet E, Avril T.
      Endoplasmic reticulum (ER) proteostasis is often altered in tumor cells due to intrinsic (oncogene expression, aneuploidy) and extrinsic (environmental) challenges. ER stress triggers the activation of an adaptive response named the Unfolded Protein Response (UPR), leading to protein translation repression, and to the improvement of ER protein folding and clearance capacity. The UPR is emerging as a key player in malignant transformation and tumor growth, impacting on most hallmarks of cancer. As such, the UPR can influence cancer cells' migration and invasion properties. In this review, we overview the involvement of the UPR in cancer progression. We discuss its cross-talks with the cell migration and invasion machinery. Specific aspects will be covered including extracellular matrix (ECM) remodeling, modification of cell adhesion, chemo-attraction, epithelial-mesenchymal transition (EMT), modulation of signaling pathways associated with cell mobility, and cytoskeleton remodeling. The therapeutic potential of targeting the UPR to treat cancer will also be considered with specific emphasis in the impact on metastasis and tissue invasion.
    Keywords:  ATF6; ER stress; IRE1; PERK; cancer; cell invasion; cell migration
    DOI:  https://doi.org/10.3390/cancers11050631
  2. J Clin Med. 2019 May 08. pii: E624. [Epub ahead of print]8(5):
    Santamaría PG, Mazón MJ, Eraso P, Portillo F.
      The endoplasmic reticulum (ER) is the organelle where newly synthesized proteins enter the secretory pathway. Different physiological and pathological conditions may perturb the secretory capacity of cells and lead to the accumulation of misfolded and unfolded proteins. To relieve the produced stress, cells evoke an adaptive signalling network, the unfolded protein response (UPR), aimed at recovering protein homeostasis. Tumour cells must confront intrinsic and extrinsic pressures during cancer progression that produce a proteostasis imbalance and ER stress. To overcome this situation, tumour cells activate the UPR as a pro-survival mechanism. UPR activation has been documented in most types of human tumours and accumulating evidence supports a crucial role for UPR in the establishment, progression, metastasis and chemoresistance of tumours as well as its involvement in the acquisition of other hallmarks of cancer. In this review, we will analyse the role of UPR in cancer development highlighting the ability of tumours to exploit UPR signalling to promote epithelial-mesenchymal transition (EMT).
    Keywords:  endoplasmic reticulum stress; epithelial-mesenchymal transition; metastasis; plasticity; unfolded protein response
    DOI:  https://doi.org/10.3390/jcm8050624
  3. Can J Physiol Pharmacol. 2019 May 07. 1-13
    Groenendyk J, Fan X, Peng Z, Kurgan L, Michalak M.
      Stress responses are important to human physiology and pathology, and the inability to adapt to cellular stress leads to cell death. To mitigate cellular stress and re-establish homeostasis, cells, including those in the cardiovascular system, activate stress coping response mechanisms. The endoplasmic reticulum, a component of the cellular reticular network in cardiac cells, mobilizes so-called endoplasmic reticulum stress coping responses, such as the unfolded protein response. MicroRNAs play an important part in the maintenance of cellular and tissue homeostasis, perform a central role in the biology of the cardiac myocyte, and are involved in pathological cardiac function and remodeling. In this paper, we review a link between endoplasmic reticulum homeostasis and microRNA with an emphasis on the impact on stress responses in the cardiovascular system.
    Keywords:  ER stress; cœur; endoplasmic reticulum; heart; microRNA; réponse UPR; réticulum endoplasmique; stress du RE; unfolded protein response
    DOI:  https://doi.org/10.1139/cjpp-2018-0720
  4. Cytokine. 2019 May 06. pii: S1043-4666(19)30108-5. [Epub ahead of print]120 130-143
    Yakin M, Seo B, Rich A.
      AIMS: Signal transducer and activator of transcription (STAT)-3 lies at the convergence point of key pathways involved in many malignancies including oral squamous cell carcinoma (OSCC). Endoplasmic reticulum stress (ERS) and the unfolded protein response have been shown to be involved in the pathogenesis and progression of different cancers by influencing key cellular processes such as apoptosis. We investigated the differential expression of STAT3 pathway-related genes and proteins under ERS in OSCC.METHODS: Three normal oral keratinocyte (NOK) and three OSCC cell lines were subjected to tunicamycin to induce ERS for 24 h or to the vehicle medium as control. A pathway-focussed array was used to analyse the modulation of STAT3 pathway gene expression under ERS using qPCR. The expression of key regulated proteins was investigated in the cell lines using immunocytochemistry and in 76 OSCC and 9 normal oral mucosa (NOM) tissue samples using tissue microarray technology and immunohistochemistry.
    RESULTS: ERS resulted in up-regulation of interleukin-6 receptor (IL6R) gene in NOK cell lines (p = 0.001) and IL5 (p = 0.005) and IL22 (p = 0.024) in OSCC cell lines. Greater STAT3 (p = 0.019) and leukaemia inhibitory factor receptor (p = 0.042) protein expression was observed in treated than untreated NOK cell lines.
    CONCLUSIONS: The gene and protein regulation patterns show that ERS plays a role in modifying the tumour microenvironment in OSCC by up-regulating tumour-promoting cytokines.
    Keywords:  Cancer biology; Cell signalling; Cytokines; ER stress; Oral carcinogenesis; STAT3; Tissue microarray
    DOI:  https://doi.org/10.1016/j.cyto.2019.04.013