2. Academic Validation
  3. Loss of EMP1 promotes the metastasis of human bladder cancer cells by promoting migration and conferring resistance to ferroptosis through activation of PPAR gamma signaling

Loss of EMP1 promotes the metastasis of human bladder cancer cells by promoting migration and conferring resistance to ferroptosis through activation of PPAR gamma signaling

  • Free Radic Biol Med. 2022 Aug 20;189:42-57. doi: 10.1016/j.freeradbiomed.2022.06.247.
Sha Liu 1,  Jiazhong Shi 2,  Liwei Wang 3,  Yaqin Huang 4,  Baixiong Zhao 5,  Hua Ding 6,  Yuting Liu 7,  Wuxing Wang 8,  Zhiwen Chen 9,  Jin Yang 10
Affiliations

Affiliations

  • 1 Department of Cell Biology, Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 2 Department of Cell Biology, Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 3 Department of Urology, The First Affiliated Hospital of the Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 4 Department of Cell Biology, Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 5 Department of Urology, The First Affiliated Hospital of the Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 6 Department of Urology, The First Affiliated Hospital of the Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 7 Department of Urology, The First Affiliated Hospital of the Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 8 Department of Cell Biology, Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 9 Department of Urology, The First Affiliated Hospital of the Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 10 Department of Cell Biology, Third Military Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 35850179 DOI: 10.1016/j.freeradbiomed.2022.06.247
Abstract

Metastasis, in which Cancer cells detach from the original site and colonise other organs, is the primary cause of death induced by bladder Cancer (BCa). Epithelial Membrane Protein 1 (EMP1) is dysregulated in many human cancers, and its clinical significance and biological function in diseases, including BCa, are largely unclear. Here, we demonstrated that EMP1 was downregulated in BCa cells. The deficiency of EMP1 promotes migration and confers resistance to Ferroptosis/oxidative stress in BCa cells, favouring tumour cell metastasis. Mechanistically, we demonstrated that EMP1 deficiency enhanced tumour metastasis by increasing PPARG expression and promoting its activation, leading to upregulation of pFAK(Y397) and SLC7A11, which promoted cell migration and anti-ferroptotic cell death respectively. Moreover, we found EMP1-deficient sensitized cells to PPARG's ligand, which effect are metastatic phenotype promoted and could be mitigated by FABP4 knockdown. In conclusion, our study, for the first time, reveals that EMP1 deficiency promotes BCa cell migration and confers resistance to Ferroptosis/oxidative stress, thus promoting metastasis of BCa via PPARG. These results revealed a novel role of EMP1-mediated PPARG in bladder Cancer metastasis.

Keywords

Bladder cancer; EMP1; FABP4; Metastasis; PPAR-gamma (PPARG).

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