Table 6.
Summary of cellular consequences resulting from interactions between different USPs and target proteins associated with receptor tyrosine kinases signaling pathways.
| USPs | Targets | Cell Model Association | Effects | Refs |
|---|---|---|---|---|
| USP8 | EGFR, ERBB3 and c-Met |
Mouse embryonic fibroblasts (MEFs) # | Inhibition of cellular proliferation in USP8-deficient MEFs | [161] |
| H1975 and H1650 (non-small cell lung cancer cells resistant to gefitinib) CCD-8Lu (lung fibroblasts) # HBTEC (human bronchial/tracheal epithelial cells) # |
USP8 knockdown reduces cell viability of gefitinib-resistant cells, but not in non-tumoral lung cells | [163] | ||
| LRIG1 (c-Met regulation) |
EBC1 cells (lung squamous cell carcinoma) |
USP8 overexpression reduces LRIG1—c-Met degradation induced by SAIT301 | [164] | |
| EGFR | PL16T cells (lung adenocarcinoma) |
Overexpression of USP8 increases EGFR activity and cellular proliferation | [165] | |
| VEGFR2 | HUVEC (human umbilical vein endothelial cells) # |
USP8 knockdown impaired VEGF-A signaling via proteolysis of VEGFR2 into a 120 kDa VEGFR2 fragment | [166] | |
| USP9x | Eps15 (EGFR) | HeLa cells (cervical adenocarcinoma) |
USP9x indirectly deregulates EGFR signaling; USP9x increases Eps15 monoubiquitination, supporting EGFR internalization and delaying EGFR signaling | [167] |
| USP18 | miR-7 (EGFR) | T98G (glioblastoma) HeLa (cervival adenocarcinoma) |
USP18 knockdown increases miR-7 activity, decreases EGFR levels as well as cellular proliferation and induces apoptosis | [159] |
#, The cells used were not cancer-derived cells.