Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway
Abstract Hypoxia is a typical hallmark of solid tumors and plays a crucial role in the progression of esophageal squamous cell carcinogenesis (ESCC). Nevertheless, the precise mechanisms underlying the involvement of hypoxia in tumor development remain unclear. In the present study, a novel hypoxia‐...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406674 |
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| author | Sisi Wei Xinyi Fan Xiaoya Li Wei Zhou Zhihua Zhang Suli Dai Huilai Lv Yueping Liu Baoen Shan Lianmei Zhao Qimin Zhan Yongmei Song |
| author_facet | Sisi Wei Xinyi Fan Xiaoya Li Wei Zhou Zhihua Zhang Suli Dai Huilai Lv Yueping Liu Baoen Shan Lianmei Zhao Qimin Zhan Yongmei Song |
| author_sort | Sisi Wei |
| collection | DOAJ |
| description | Abstract Hypoxia is a typical hallmark of solid tumors and plays a crucial role in the progression of esophageal squamous cell carcinogenesis (ESCC). Nevertheless, the precise mechanisms underlying the involvement of hypoxia in tumor development remain unclear. In the present study, a novel hypoxia‐induced long noncoding RNA (lncRNA) is identified first, lnc191, which is highly expressed in clinical ESCC tissues and is positively correlated with poor prognosis of ESCC patients. These findings provide evidence that the hypoxia‐inducible factor‐1α (HIF‐1α)‐mediated transcriptional activation of lnc191 enhances the growth and metastasis of ESCC cells both in vitro and in vivo. Mechanistically, lnc191 interacts with GRP78 (78‐kDa glucose‐regulated protein), one of the endoplasmic reticulum chaperone proteins, leading to its translocation to the membrane, where GRP78 binds with EGFR and enhances its phosphorylation (Y845), further activates ERK/MAPK signaling pathway, and thereby in favor of the progression of ESCC. Overall, this data proposes lnc191 as a key driver during the development of ESCC and reveals the participation of the activated GRP78/ERK/MAPK axis in the ESCC progression mediated by lnc191. These findings indicate the potential of lnc191 as a promising diagnostic biomarker and therapeutic target in ESCC. |
| format | Article |
| id | doaj-art-9f64f4e189314deeb3b5f69e313d8d0c |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-9f64f4e189314deeb3b5f69e313d8d0c2025-01-29T09:50:19ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202406674Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK PathwaySisi Wei0Xinyi Fan1Xiaoya Li2Wei Zhou3Zhihua Zhang4Suli Dai5Huilai Lv6Yueping Liu7Baoen Shan8Lianmei Zhao9Qimin Zhan10Yongmei Song11State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 ChinaState Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 ChinaResearch Center the Fourth Hospital of Hebei Medical University Jiankang Road 12 Shijiazhuang Hebei 050011 ChinaHangzhou Institute of Medicine University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Hangzhou Zhejiang 310022 ChinaNeurosurgery Department Tsinghua University Yuquan Hospital Beijing 100049 ChinaResearch Center the Fourth Hospital of Hebei Medical University Jiankang Road 12 Shijiazhuang Hebei 050011 ChinaDepartment of Thoracic Surgery the Fourth Hospital of Hebei Medical University Shijiazhuang Hebei 050011 ChinaPathology Department the Fourth Hospital of Hebei Medical University Shijiazhuang Hebei 050011 ChinaResearch Center the Fourth Hospital of Hebei Medical University Jiankang Road 12 Shijiazhuang Hebei 050011 ChinaState Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 ChinaKey Laboratory of Carcinogenesis and Translational Research Laboratory of Molecular Oncology Peking University Cancer Hospital & Institute Beijing 100142 ChinaState Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 ChinaAbstract Hypoxia is a typical hallmark of solid tumors and plays a crucial role in the progression of esophageal squamous cell carcinogenesis (ESCC). Nevertheless, the precise mechanisms underlying the involvement of hypoxia in tumor development remain unclear. In the present study, a novel hypoxia‐induced long noncoding RNA (lncRNA) is identified first, lnc191, which is highly expressed in clinical ESCC tissues and is positively correlated with poor prognosis of ESCC patients. These findings provide evidence that the hypoxia‐inducible factor‐1α (HIF‐1α)‐mediated transcriptional activation of lnc191 enhances the growth and metastasis of ESCC cells both in vitro and in vivo. Mechanistically, lnc191 interacts with GRP78 (78‐kDa glucose‐regulated protein), one of the endoplasmic reticulum chaperone proteins, leading to its translocation to the membrane, where GRP78 binds with EGFR and enhances its phosphorylation (Y845), further activates ERK/MAPK signaling pathway, and thereby in favor of the progression of ESCC. Overall, this data proposes lnc191 as a key driver during the development of ESCC and reveals the participation of the activated GRP78/ERK/MAPK axis in the ESCC progression mediated by lnc191. These findings indicate the potential of lnc191 as a promising diagnostic biomarker and therapeutic target in ESCC.https://doi.org/10.1002/advs.202406674EGFRESCCGRP78LncRNAMAPK |
| spellingShingle | Sisi Wei Xinyi Fan Xiaoya Li Wei Zhou Zhihua Zhang Suli Dai Huilai Lv Yueping Liu Baoen Shan Lianmei Zhao Qimin Zhan Yongmei Song Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway Advanced Science EGFR ESCC GRP78 LncRNA MAPK |
| title | Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway |
| title_full | Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway |
| title_fullStr | Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway |
| title_full_unstemmed | Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway |
| title_short | Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway |
| title_sort | hypoxia induced lnc191 upregulation dictates the progression of esophageal squamous cell carcinoma by activating grp78 erk pathway |
| topic | EGFR ESCC GRP78 LncRNA MAPK |
| url | https://doi.org/10.1002/advs.202406674 |
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