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. 2024 May 23;5(6):e554. doi: 10.1002/mco2.554

FIGURE 3.

FIGURE 3

CD44‐mediated cancer‐associated signaling pathways. CD44 can contribute to cancer invasion, migration, and metastasis through Hippo–YAP, HIF‐1α, and Wnt–FoxM1–Twist signaling. CD44v3 binds to CHI3L1, resulting in metastasis of GC via the ERK–AKT–Wnt pathway. Silencing of CD44v6 blocks PI3K/AKT/GSK3β signaling pathway, EMP1‐affected CD44 expression inhibits the PI3K/AKT signaling pathways, CD44 inhabits the phosphorylation of AKT/mTOR, HA‐induced CD44 interaction with C‐Src‐activated Twist can result in inhibiting cancer aggressive behavior. The TWIST1–CD44–MMP13 axis involves in tumor aggressiveness through EMT. MiR‐302a binds to CD44, resulting in suppressing CSCs‐like properties via EGFR‐mediated MAPK and AKT signaling. CD44high CSCs activate the AKT and MAPK pathways via the expression of HNRNPA2B1, CD44 activates KRAS/ERK signaling, EDH1 interaction with CD44 inhabiting Hippo pathway, the upregulation of CD44 activates YAP through inactivation of Hippo signaling pathway, CD44ICD binding to HIF‐2α via activation of HIF‐targeting genes, and the ubiquitination and degradation of CD44/cortactin via activating Wnt/β‐catenin signaling can result in cancer stemness and EMT features. Ablation of CD44v via activation of p38 signaling and Vitamin D receptor‐induced inhibition of CD44 via Wnt/β‐catenin signaling can result in inhabiting tumor growth and cell proliferation. CD44v10 activates ERK/p38 MAPK and AKT/mTOR signaling, the TM4SF5/CD44 interaction via activating c‐Src/STAT3/Twist1/Bmi1 signaling can result in facilitating cell proliferation. Reducing the glycolytic phenotype of cancer cells through the c‐Src/AKT/LKB1/AMPKα/HIF‐1α signaling pathway can silence CD44 to regulate cell proliferation. CD44 collaborates with ERBB2 to promote the radioresistance of cancer cells via p38 phosphorylation. CD44+ cancer cells reverse sorafenib resistance via suppressing Hedgehog signaling. Upregulation of CD44 confers chemoresistance via β‐catenin/p53/p21, which is associated with the secretory mucin MUC5AC. This scheme was generated using Biorender.