Table 2 Functions of USP28 in cancers
From: Ubiquitin-specific protease 28: the decipherment of its dual roles in cancer development
Effect of USP28 | Effect of USP28 on cancer hallmarks | Cancer type | Related mechanisms | The effects of USP28 expression in cancer prognosis | References |
|---|---|---|---|---|---|
Promoting cancers | Promoting cell proliferation | Ovarian clear cell carcinoma | HNF-1β upregulates USP28, which gives rise to the high level of Claspin and CHK1 after the treatment of bleomycin | – | [37] |
High grade serous ovarian cancer | USP28 increases the level of Cyclin E1, which then promotes cell cycle | – | [34] | ||
Squamous cancer | Elevated USP28 upregulates ΔNp63 and participates in the process of pro-cancer with mediation of ΔNp63 | Negative | [15] | ||
Pancreatic cancer | USP28 stabilizes FOXM1 and then leads to the activation of Wnt/β-catenin pathway | Negative | [4] | ||
Lung cancer | USP28 deubiquitinates c-Myc, through which the activation of Cyclin D1-CDK6 complex is promoted. c-Myc is stabilized by USP28 and then increases HK2, PKM2 and LDHA, stimulating aerobic glycolysis | – | [14] | ||
USP28 enhances STAT3 signaling | Negative | [33] | |||
Breast cancer | Overexpression of HDAC5 reduces the polyubiquitination of USP28, contributing to the increase of LSD1 | – | [55] | ||
Colorectal cancer | USP28 maintains the expression of FOXC1 and then leads to the decrease of FBP1, enhancing aerobic glycolysis | – | [71] | ||
– | Lin28A brings about more colonies with the help of USP28 | – | [74] | ||
Initiating invasion and metastasis | Gastric cancer | USP28 contributes to higher N-cadherin while lower E-cadherin, leading to the stimulation of EMT | – | [83] | |
USP28 stabilizes Snail proteins which may then suppresses E-cadherin | – | ||||
– | Deubiquitination of Lin28A caused by USP28 promotes metastasis | – | [74] | ||
Breast cancer | Stabilization of LSD1 mediates the process that USP28 inhibits CLDN7 | – | [55] | ||
Inhibiting cell differentiation | Colorectal cancer | USP28 stabilizes NICD1 and maintain the activation of Notch signaling, leading to the suppression of cell differenciation | Negative | [35] | |
Breast cancer | USP28 deubiquitinates LSD1, and then differentiation gene p21Cif1/Waf1 reduces while pluripotency markers SOX2 and Oct4 increases | – | [9] | ||
– | USP28 enhances the suppression of let-7 induced by Lin28A, contributing to the suppression of cell differentiation | – | [74] | ||
Inducing angiogenesis | – | USP28 antagonizes the impact of FBW7 and inhibits the ubiquitination of HIF-1α | – | [25] | |
Esophageal cancer | c-Myc can be deubiquitinated by USP28 and then results in the accumulation of HIF-1α | – | [97] | ||
Maintaining cancer stem cell-like characteristics | Bladder cancer | Through upregulation USP28, ATG7 promotes the expression of CD44 | - | [36] | |
Breast cancer | USP28 contributes to the stabilization of c-myc, which stimulates the upregulation of SLUG and then maintains CSCs mediated by SOX9 | - | |||
USP28-LSD1 axis protects characteristics of CSCs | – | [9] | |||
Inhibiting cancers | Inhibiting cell proliferation | – | Knockdown of caspase-8 facilitates activation of USP28 which then brings about p53 stabilization | – | [26] |
|  | – | USP28 decreases ub-K119-H2A, leading to the elevation of p53, p21 and p16INK4A | – | [32] | |
– | USP28 turns over the ubiquitination of Plk3 possessing the ability to activate CHK2 and p53 | – | [111] | ||
Melanoma | USP28 reverses the auto-ubiquitination of FBW7, resulting in the decrease of BRAF and weakness of MAPK signaling | Positive | [16] | ||
Suppressing tumor invasion and metastasis | Breast cancer | USP28 reduces the accumulation of α-SMA while increases E-cadherin | Positive | [10] | |
Overexpression of USP28 leads to decrease of FN-1 and elevation of E-cadherin | – | [40] | |||
Melanoma | USP28 reverses the auto-ubiquitination of FBW7, resulting in the decrease of BRAF and weakness of MAPK signaling | Positive | [16] |