2. Academic Validation
  3. Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway

Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway

  • Adv Sci (Weinh). 2025 Jan;12(4):e2406674. doi: 10.1002/advs.202406674.
Sisi Wei 1 2 3,  Xinyi Fan 1,  Xiaoya Li 2 3,  Wei Zhou 4,  Zhihua Zhang 5,  Suli Dai 2 3,  Huilai Lv 6,  Yueping Liu 7,  Baoen Shan 2 3,  Lianmei Zhao 1 2 3,  Qimin Zhan 8,  Yongmei Song 1
Affiliations

Affiliations

  • 1 State 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, China.
  • 2 Research Center, the Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang, Hebei, 050011, China.
  • 3 Key Laboratory of Tumor Prevention and Precision Diagnosis and Treatment of Hebei, Clinical Oncology Research Center, Shijiazhuang, Hebei, 050011, China.
  • 4 Hangzhou Institute of Medicine, University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China.
  • 5 Neurosurgery Department, Tsinghua University Yuquan Hospital, Beijing, 100049, China.
  • 6 Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
  • 7 Pathology Department, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
  • 8 Key Laboratory of Carcinogenesis and Translational Research, Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
PMID: 39629920 DOI: 10.1002/advs.202406674
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.

Keywords

EGFR; ESCC; GRP78; LncRNA; MAPK.

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