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Tumor Discovery WDR4 in cancer

Figure 2. Molecular mechanisms of WDR4 in tumorigenesis. WDR4 can ubiquitinate and degrade multiple important proteins such as PML, PTPN23, and
P53. It can also form a complex with METTL1 as a reader of M7G modification, promoting various types of cancers.
Abbreviations: ACC: Adrenocortical carcinoma; ARNT: Aryl hydrocarbon receptor nuclear translocator; EGFR: Epidermal growth factor receptor;
ESCC: Esophageal squamous cell carcinoma; LIHC: Liver hepatocellular carcinoma; LUSC: Lung squamous cell carcinoma; METTL1: Methyltransferase
like 1; PML: Promyelocytic leukemia; PRAD: Prostate adenocarcinoma; PTPN23: Protein tyrosine phosphatase non-receptor type 23; SAA2: Serum
amyloid A2; TNBC: Triple-negative breast cancer; uPAR: Urokinase-type plasminogen activator receptor; WDR4: WD repeat domain 4.

Figure 3. Molecular mechanisms underlying the inhibitory effects of WDR4 on the cell cycle and apoptosis of cancer cells.
Abbreviations: Bak: Bcl-2-associated x protein; Bax: Bcl-2-associated x protein; BCL-2: B-cell lymphoma 2; CDC25C: Cell division cycle 25C; WDR4: WD
repeat domain 4.

derivatives, primarily initiating downstream signaling by thus activating AKT. This process is a core step in the PI3K/
45
generating phosphoinositide (3,4,5)-trisphosphate (PIP3) AKT/mTOR signaling pathway. Through the activation of
on the cell membrane. 43,44 PI3K activates this signaling AKT, this pathway regulates multiple cellular functions,
pathway by interacting with receptor proteins on the cell including protein synthesis, metabolic regulation, cell
membrane, such as growth factor receptors. cycle control, and anti-apoptotic actions. Moreover, the
PI3K phosphorylates phosphoinositides on the cell PI3K/AKT/mTOR pathway plays an essential role in the
membrane to produce PIP3, and the accumulation of PIP3 initiation and progression of various cancers by regulating
provides binding sites for downstream kinases like AKT, cell proliferation and survival. 46

Volume 4 Issue 1 (2025) 40 doi: 10.36922/td.5830