Decreasing expression of glucose‐regulated protein GRP78/BiP as a significant prognostic predictor in patients with advanced laryngeal squamous cell carcinoma

Kaira, Kyoichi; Toyoda, Minoru; Shimizu, Akira; Imai, Hisao; Sakakura, Koichi; Nikkuni, Osamu; Suzuki, Masami; Iijima, Misa; Asao, Takayuki; Chikamatsu, Kazuaki

doi:10.1002/hed.24471

Cited by 16 publications

(6 citation statements)

References 17 publications

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“…It has been revealed to confer tumor resistance to chemotherapeutic agents and radiation therapy ( 17 , 18 ). The GRP78 expression and distribution changes have been observed in multiple instances, including thrombotic disease and cancer ( 19 , 20 ). It had been demonstrated that GRP78 is highly expressed in many tumors, thereby suggesting that it may play a vital role in tumor biology ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

miR‑495 enhances the efficacy of radiotherapy by targeting GRP78 to regulate EMT in nasopharyngeal carcinoma cells

Feng

Wang

et al. 2018

Oncol Rep

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Glucose-regulated protein 78 (GRP78) was revealed to be associated with the radioresistance of nasopharyngeal carcinoma (NPC) in our previous study. GRP78 is a highly expressed cell surface protein, and holds great promise as a cancer specific target. Its expression may be impacted by the regulation of miRNAs, which may be involved in the radioresistance of NPC. A better understanding of the mechanisms of radioresistance may generate new targets of therapy for NPC patients. The present study was designed to investigate the effect of microRNA targeting GRP78 on the radiosensitivity of NPC. First, we used miRWalk software to predict miRNAs that may interact with GRP78. Subsequently, analysis of miR-495 and GRP78 expression was performed in the primary tissues of 92 NPC tissues and cell lines by immunohistochemistry and real-time PCR and the results revealed that miR-495 expression was lower in radioresistant NPC tissues in comparison to chronic rhinitis tissues, and also lower in radioresistant 5-8F cells (5-8F-IR) in comparison to its parental 5-8F cells. Notably, we observed an inverse association between the expression miR-495 and GRP78. Our bioinformatics analysis led to the identification of miR-495 as the optimal miRNA interacting with GRP78 mRNA. Furthermore, miR-495 targeting the 3′untranslated region (UTR) of GRP78 was detected by a Dual-Glo Luciferase Assay system. Finally, we observed that miR-495 inhibition led to a significant increase in the radioresistance of 5-8F cells and higher GRP78 expression, which may be involved in epithelial-mesenchymal transition (EMT) phenotype. miR-495 targeted the 3′UTR of GRP78 and contributed to the efficacy of radiation therapy in NPC.

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Section: Discussionmentioning

confidence: 99%

miR‑495 enhances the efficacy of radiotherapy by targeting GRP78 to regulate EMT in nasopharyngeal carcinoma cells

Feng

Wang

et al. 2018

Oncol Rep

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“…Elevated levels of GRP78 were associated with metastatic potential in numerous cancers [20,21,22]. Overexpressed GRP78 in patient samples are frequently detected in HNSCC [23,24], including nasopharyngeal carcinoma (NPC) [25], oral lesions [26], laryngeal SCC [27], tongue cancer [28] and advanced hypopharyngeal squamous cell carcinomas (HSCC) [24]. Samples with the lowest GRP78 expression were associated with advanced stage of OSCC and neck lymph node metastasis [29].…”

Section: Linking Hnscc Carcinogenesis To the Uprmentioning

confidence: 99%

“…For example, GRP78 overexpression positively correlates with a more aggressive potential and poor survival in oral lesions [26] and tongue cancer [28], suggesting that GRP78 may be a prognostic factor in these two cancer types. In contrast, the highest GRP78 expression in HSCC patients or laryngeal SCC patients with advanced disease was found to contribute to better survival [24,27]. The origin of this discrepancy in survival remains to be explored, in particular the impact of GRP78 localization, since this chaperone can be found in the ER lumen, as well as on the cell surface of tumor cells [30].…”

Section: Linking Hnscc Carcinogenesis To the Uprmentioning

confidence: 99%

Impact and Relevance of the Unfolded Protein Response in HNSCC

Pluquet

Galmiche

2019

IJMS

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Head and neck squamous cell carcinomas (HNSCC) encompass a heterogeneous group of solid tumors that arise from the upper aerodigestive tract. The tumor cells face multiple challenges including an acute demand of protein synthesis often driven by oncogene activation, limited nutrient and oxygen supply and exposure to chemo/radiotherapy, which forces them to develop adaptive mechanisms such as the Unfolded Protein Response (UPR). It is now well documented that the UPR, a homeostatic mechanism, is induced at different stages of cancer progression in response to intrinsic (oncogenic activation) or extrinsic (microenvironment) perturbations. This review will discuss the role of the UPR in HNSCC as well as in the key processes that characterize the physiology of HNSCC. The role of the UPR in the clinical context of HNSCC will also be addressed.

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“…GRP78 upregulation in multiple human tumors contributes to tumor cell survival and chemoresistance through high tolerance for ER stress while its suppression leads to enhanced cytotoxic response to chemotherapeutic drugs [13][14][15][16]41]. Increased GRP78 expression is associated with higher pathological grades, high risk of recurrence, and poor prognosis of cancer patients [41][42][43][44][45]. Therefore, GRP78 has been suggested as a target for therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

XAF1 drives apoptotic switch of endoplasmic reticulum stress response through destabilization of GRP78 and CHIP

et al. 2022

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X-linked inhibitor of apoptosis-associated factor-1 (XAF1) is a stress-inducible tumor suppressor that is commonly inactivated in many human cancers. Despite accumulating evidence for the pro-apoptotic role for XAF1 under various stressful conditions, its involvement in endoplasmic reticulum (ER) stress response remains undefined. Here, we report that XAF1 increases cell sensitivity to ER stress and acts as a molecular switch in unfolded protein response (UPR)-mediated cell-fate decisions favoring apoptosis over adaptive autophagy. Mechanistically, XAF1 interacts with and destabilizes ER stress sensor GRP78 through the assembly of zinc finger protein 313 (ZNF313)-mediated destruction complex. Moreover, XAF1 expression is activated through PERK-Nrf2 signaling and destabilizes C-terminus of Hsc70-interacting protein (CHIP) ubiquitin E3 ligase, thereby blocking CHIP-mediated K63-linked ubiquitination and subsequent phosphorylation of inositol-required enzyme-1α (IRE1α) that is involved in in the adaptive ER stress response. In tumor xenograft assays, XAF1−/− tumors display substantially lower regression compared to XAF1+/+ tumors in response to cytotoxic dose of ER stress inducer. XAF1 and GRP78 expression show an inverse correlation in human cancer cell lines and primary breast carcinomas. Collectively this study uncovers an important role for XAF1 as a linchpin to govern the sensitivity to ER stress and the outcomes of UPR signaling, illuminating the mechanistic consequence of XAF1 inactivation in tumorigenesis.

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Decreasing expression of glucose‐regulated protein GRP78/BiP as a significant prognostic predictor in patients with advanced laryngeal squamous cell carcinoma

Cited by 16 publications

References 17 publications

miR‑495 enhances the efficacy of radiotherapy by targeting GRP78 to regulate EMT in nasopharyngeal carcinoma cells

miR‑495 enhances the efficacy of radiotherapy by targeting GRP78 to regulate EMT in nasopharyngeal carcinoma cells

Impact and Relevance of the Unfolded Protein Response in HNSCC

XAF1 drives apoptotic switch of endoplasmic reticulum stress response through destabilization of GRP78 and CHIP

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