title: Construction of a CXCL12-KDEL fusion gene to inhibit head and neck squamous cell carcinoma metastasis by intracellular sequestration of CXCR4.
abstract: The CXCL12-CXCR4 biological axis consisting of the chemotactic factor CXCL12 and its specific receptor CXCR4 plays an important role in oral cancer metastasis. High expression of CXCR4 may help oral squamous cancer cells invade local tissues and metastasize to lymph nodes. No obvious association was observed between CXCL12 expression and lymph node metastasis, suggesting that CXCL12 chemotaxis may only be related to CXCR4 expression on the tumor cell membrane. KDEL can be retained by receptors on the surface of the intracellular endoplasmic reticulum (ER) and also be called an ER retention signal sequence. So we adopted the KDEL sequence in this study to generate a CXCL12-KDEL fusion protein in combination with a traceable E-tag label. As such, CXCL12 was retained in the ER. Specific receptor CXCR4 binds to the CXCL12-KDEL, was also retained in the ER, and was thus prevented from reaching the oral squamous cancer cell surface. We reduced the cell surface level of CXCR4 and called the technique "intracellular sequestration." By this way, we have finished blocking of CXCL12-CXCR4 biological axis and inhibiting lymph node metastasis of oral carcinoma.
authors: Department of Maxillofacial and ENT, National Cancer Clinical Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
authors: Wenchao
authors: W
authors: Zhang
authors: Department of Maxillofacial and ENT, National Cancer Clinical Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
authors: Xudong
authors: X
authors: Wang
authors: Department of Maxillofacial and ENT, National Cancer Clinical Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
authors: Kai
authors: K
authors: Yue
authors: Department of Maxillofacial and ENT, National Cancer Clinical Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
authors: Su
authors: S
authors: Liu
authors: Department of Maxillofacial and ENT, National Cancer Clinical Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
authors: Xiaonan
authors: X
authors: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; C064459:KDEL receptor; D019718:Receptors, CXCR4; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins