Abstract B040: Imiquimod initiates tumor specific overload of the ER stress response in Tasmanian devil facial cancer cells

2016 ◽  
Author(s):  
Amanda L. Patchett ◽  
Terry L. Pinfold ◽  
Cesar Tovar ◽  
Bruce Lyons ◽  
Gregory M. Woods
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Cancer Cells ◽  
Tasmanian Devil ◽  
Er Stress Response

scholarly journals Targeting the IRE1α/XBP1s pathway suppresses CARM1-expressing ovarian cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianhuang Lin ◽  
Heng Liu ◽  
Takeshi Fukumoto ◽  
Joseph Zundell ◽  
Qingqing Yan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stress Response ◽  
Er Stress ◽  
Cancer Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Er Stress Response

AbstractCARM1 is often overexpressed in human cancers including in ovarian cancer. However, therapeutic approaches based on CARM1 expression remain to be an unmet need. Cancer cells exploit adaptive responses such as the endoplasmic reticulum (ER) stress response for their survival through activating pathways such as the IRE1α/XBP1s pathway. Here, we report that CARM1-expressing ovarian cancer cells are selectively sensitive to inhibition of the IRE1α/XBP1s pathway. CARM1 regulates XBP1s target gene expression and directly interacts with XBP1s during ER stress response. Inhibition of the IRE1α/XBP1s pathway was effective against ovarian cancer in a CARM1-dependent manner both in vitro and in vivo in orthotopic and patient-derived xenograft models. In addition, IRE1α inhibitor B-I09 synergizes with immune checkpoint blockade anti-PD1 antibody in an immunocompetent CARM1-expressing ovarian cancer model. Our data show that pharmacological inhibition of the IRE1α/XBP1s pathway alone or in combination with immune checkpoint blockade represents a therapeutic strategy for CARM1-expressing cancers.

scholarly journals WWOX sensitises ovarian cancer cells to paclitaxel via modulation of the ER stress response

2017 ◽  
Vol 8 (7) ◽  
pp. e2955-e2955 ◽  
Author(s):  
Szymon Janczar ◽  
Jaya Nautiyal ◽  
Yi Xiao ◽  
Edward Curry ◽  
Mingjun Sun ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stress Response ◽  
Er Stress ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Er Stress Response

scholarly journals Androgen-induced expression of endoplasmic reticulum (ER) stress response genes in prostate cancer cells

Oncogene ◽  
2002 ◽  
Vol 21 (57) ◽  
pp. 8749-8758 ◽  
Author(s):  
Takehiko Segawa ◽  
Martin E Nau ◽  
Linda L Xu ◽  
Rao N Chilukuri ◽  
Mazen Makarem ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Induced Expression ◽  
Er Stress Response ◽  
Stress Response Genes

scholarly journals Induction of Endoplasmic Reticulum-induced Stress Genes in Panc-1 Pancreatic Cancer Cells Is Dependent on Sp Proteins

2005 ◽  
Vol 280 (16) ◽  
pp. 16508-16513 ◽  
Author(s):  
Maen Abdelrahim ◽  
Shengxi Liu ◽  
Stephen Safe
Keyword(s):  
Pancreatic Cancer ◽  
Endoplasmic Reticulum ◽  
Transcription Factors ◽  
Stress Response ◽  
Er Stress ◽  
Cancer Cells ◽  
Gene Promoters ◽  
Er Stress Response ◽  
Pancreatic Cancer Cells ◽  
Pharmacologically Active

Endoplasmic reticulum (ER) stress plays a critical role in multiple diseases, and pharmacologically active drugs can induce cell death through ER stress pathways. Stress-induced genes are activated through assembly of transcription factors on ER stress response elements (ERSEs) in target gene promoters. Gel mobility shift and chromatin immunoprecipitation assays have confirmed interactions of NF-Y and YY1 with the distal motifs of the tripartite ERSE from the glucose-related protein 78 (GRP78) gene promoter. The GC-rich nonanucleotide (N9) sequence, which forms the ER stress response binding factor (ERSF) complex binds TFII-I and ATF6; however, we have now shown that in Panc-1 pancreatic cancer cells, this complex also binds Sp1, Sp3, and Sp4 proteins. Sp proteins are constitutively bound to the ERSE; however, activation of GRP78 protein (or reporter gene) by thapsigargin or tunicamycin is inhibited after cotransfection with small inhibitory RNAs for Sp1, Sp3, and Sp4. This study demonstrates that Sp transcription factors are important for stress-induced responses through their binding to ERSEs.

Self-delivery of N-hydroxylethyl peptide assemblies to the cytosol inducing endoplasmic reticulum dilation in cancer cells

2019 ◽  
Vol 55 (52) ◽  
pp. 7474-7477 ◽  
Author(s):  
Shijin Zhang ◽  
Xunwu Hu ◽  
Dingze Mang ◽  
Toshio Sasaki ◽  
Ye Zhang
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Alcohol Abuse ◽  
Er Stress ◽  
Cancer Cells ◽  
Clinical Studies ◽  
Peptide Assembly ◽  
Er Stress Response

Inspired by clinical studies on alcohol abuse induced endoplasmic reticulum disruption, we designed a N-hydroxylethyl peptide assembly to regulate the ER stress response in cancer cells.

scholarly journals Endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases

2017 ◽  
Author(s):  
Arnaud Pommier ◽  
Naishitha Anaparthy ◽  
Nicoletta Memos ◽  
Z Larkin Kelley ◽  
Alizée Gouronnec ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Cancer Cells ◽  
Ductal Adenocarcinoma ◽  
Cytokeratin 19 ◽  
Chemical Chaperone ◽  
Er Stress Response ◽  
Cancer Metastases

AbstractPatients who have had their primary pancreatic ductal adenocarcinoma (PDA) surgically resected often develop metastatic disease, exemplifying the problem of latent metastases. Livers from patients and mice with PDA contained single, disseminated cancer cells (DCCs) with an unusual phenotype of being cytokeratin-19 (CK19)- and MHC class I (MHCI)-. We created a mouse model to determine how DCCs develop, their relationship to metastatic latency, and the role of immunity. Intra-portal injection of immunogenic PDA cells into pre-immunized mice seeded livers only with single, non-replicating DCCs lacking MHCI and CK19; naïve recipients had macro-metastases. Transcriptomic analysis of PDA cells with the DCC phenotype demonstrated an endoplasmic reticulum (ER) stress response. Relieving ER stress with a chemical chaperone, in combination with T cell-depletion, stimulated outgrowth of macro-metastatic lesions containing PDA cells expressing MHCI and CK19. The ER stress response is the cell-autonomous reaction that enables DCCs to escape immunity and establish latent metastases.One sentence summary:Latent pancreatic cancer metastases are created when T cells select disseminated cancer cells in which immune resistance and quiescence have been imposed by endoplasmic stress.

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