FIGURE 7.

Schematic diagram showing the mechanism of EGFR signaling attenuation mediated by Rab21‐MFN2‐PTPRJ axis. In normal kidney epithelial cells, the interaction between MFN2 and Rab21 facilitates the mitochondria juxtaposition of internalized EGFR, where EGFR is dephosphorylated by PTPRJ, thus, attenuating the downstream signal transduction. In ccRCC cells, MFN2 deficiency leads to reduced EGFR dephosphorylation by PTPRJ in the OMM, thereby causing enhanced downstream signaling.

Abbreviations: CCRCC, clear cell renal cell carcinoma; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; P, Phosphorylation; STAT3, signal transducer and activator of transcription; AKT, protein kinase B; ERK, extracellular signal‐regulated kinase; OMM, outer mitochondrial membrane.