title: CXCL5/CXCR2 axis promotes bladder cancer cell migration and invasion by activating PI3K/AKT-induced upregulation of MMP2/MMP9.
abstract: Bladder cancer (BCa) is the most common malignant disease of the urinary tract system, yet the etiology is still poorly understood. Clinically, the majority of BCa patients progress to invasive disease at the final stage, leading to death. Previous investigations have demonstrated that matrix metal-loproteinases (MMPs) play irreplaceable roles in tumor cell extravasation and implantation. In addition, increasing numbers of reports provide evidence that MMPs, especially MMP2 and MMP9 are monitored by various signal transduction pathways targeting tumor metastasis. Seed-and-soil theory has called to attention the importance of the tumor microenvironment in disease progression. To that end, we previously reported the key role of hypoxia in BCa progression. Herein, we report the role of chemokines, specifically CXCL5, is involved in BCa development. Though it has been reported that CXCL5 promotes BCa metastasis and progression, the exact mechanisms are still unknown, necessitating the need for further investigation into the role of CXCL5 in BCa. In this study, IHC staining of BCa tumor sections showed elevated expression of CXCL5 in BCa, which correlated with disease stage. Our mechanistic studies show that CXCL5 contributes to BCa migration and invasion by binding to its receptor, CXCR2, leading to the upregulation of MMP2/MMP9 by activating PI3K/AKT signaling. This study offers vital evidence of how CXCL5 promotes BCa metastasis, and thus may potentially be used as a therapeutic target against BCa.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, P.R. China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Guan
authors.affiliation: Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, P.R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, P.R. China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, P.R. China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, P.R. China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D054365:Chemokine CXCL5 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D023063:Receptors, Interleukin-8B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9