Clinical significance of L1CAM expression and its biological role in the progression of oral squamous cell carcinoma

Kim, Jihoon; Lee, Kwang Won; Ahn, Dae‐Hwan; Oh, Keunhee; Yoon, Hye‐Jung

doi:10.3892/or.2023.8504

Cited by 7 publications

(4 citation statements)

References 40 publications

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“…Our study showed that overexpression and knockdown of ADAMTS1 respectively induced upregulation and downregulation of L1-180 in OSCC cells, Moreover, the secreted L1CAM level was also affected in ADAMTS1-manipulated OSCC cells. Furthermore, treatment with the soluble recombinant L1CAM protein (rhL1CAM) actually increased the invasive ability of OSCC cells in the present and previous studies [ 46 ]. We also observed that ADAMTS1 physically interacts with L1CAM, suggesting that ADAMTS1 might bind with L1CAM to cleave L1CAM, generate soluble L1-180, and promote invasion and LN metastasis in OSCC cells.…”

Section: Discussionsupporting

confidence: 71%

Cyclic increase in the ADAMTS1-L1CAM-EGFR axis promotes the EMT and cervical lymph node metastasis of oral squamous cell carcinoma

Chien,

Yang,

et al. 2024

Cell Death Dis

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The matrix metalloprotease A disintegrin and metalloprotease with thrombospondin motifs 1 (ADAMTS1) was reported to be involved in tumor progression in several cancer types, but its contributions appear discrepant. At present, the role of ADAMTS1 in oral squamous cell carcinoma (SCC; OSCC) remains unclear. Herein, The Cancer Genome Atlas (TCGA) database showed that ADAMTS1 transcripts were downregulated in head and neck SCC (HNSCC) tissues compared to normal tissues, but ADAMTS1 levels were correlated with poorer prognoses of HNSCC patients. In vitro, we observed that ADAMTS1 expression levels were correlated with the invasive abilities of four OSCC cell lines, HSC-3, SCC9, HSC-3M, and SAS. Knockdown of ADAMTS1 in OSCC cells led to a decrease and its overexpression led to an increase in cell-invasive abilities in vitro as well as tumor growth and lymph node (LN) metastasis in OSCC xenografts. Mechanistic investigations showed that the cyclic increase in ADAMTS1-L1 cell adhesion molecule (L1CAM) axis-mediated epidermal growth factor receptor (EGFR) activation led to exacerbation of the invasive abilities of OSCC cells via inducing epithelial-mesenchymal transition (EMT) progression. Clinical analyses revealed that ADAMTS1, L1CAM, and EGFR levels were all correlated with worse prognoses of HNSCC patients, and patients with ADAMTS1high/L1CAMhigh or EGFRhigh tumors had the shortest overall and disease-specific survival times. As to therapeutic aspects, we discovered that an edible plant-derived flavonoid, apigenin (API), drastically inhibited expression of the ADAMTS1-L1CAM-EGFR axis and reduced the ADAMTS1-triggered invasion and LN metastasis of OSCC cells in vitro and in vivo. Most importantly, API treatment significantly prolonged survival rates of xenograft mice with OSCC. In summary, ADAMTS1 may be a useful biomarker for predicting OSCC progression, and API potentially retarded OSCC progression by targeting the ADAMTS1-L1CAM-EGFR signaling pathway.

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Section: Discussionsupporting

confidence: 71%

Cyclic increase in the ADAMTS1-L1CAM-EGFR axis promotes the EMT and cervical lymph node metastasis of oral squamous cell carcinoma

Chien,

Yang,

et al. 2024

Cell Death Dis

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“…The cell adhesion receptor L1 was shown to signal in a variety of cancer cell types and in neuronal cells by different signaling pathways [42][43][44][45][46], and Mucin2 expression is regulated by several signaling pathways, including Ras, ERK, PKC, PI3K, and NF-κB signaling [47,48]. In this study, we showed that the mechanisms whereby L1 induces Mucin2 expression involve various pathways, including Wnt/β-catenin, ERK, p38, and Akt.…”

Section: Discussionmentioning

confidence: 72%

An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1

Saha,

Gavert,

Brabletz

et al. 2023

IJMS

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An induction in the expression of the cell adhesion receptor L1, a Wnt target gene, is a characteristic feature of Wnt/β-catenin activation in colon cancer cells at later stages of the disease. We investigated the proteins secreted following L1 expression in colon cancer cells and identified Mucin2 among the most abundant secreted proteins. We found that suppressing Mucin2 expression in L1-expressing colon cancer cells inhibits cell proliferation, motility, tumorigenesis, and liver metastasis. We detected several signaling pathways involved in Mucin2 induction in L1-expressing cells. In human colon cancer tissue, Mucin2 expression was significantly reduced or lost in the adenocarcinoma tissue, while in the mucinous subtype of colon cancer tissue, Mucin2 expression was increased. An increased signature of L1/Mucin2 expression reduced the survival rate of human colon cancer patients. Thus, induction of Mucin2 expression by L1 is required during mucinous colon cancer progression and can serve as a marker for diagnosis and a target for therapy.

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“…It was found that PAK5 was able to reduce the activity of the apoptotic core component Caspase-3 [ 38 ]. L1 cell adhesion molecule (L1CAM) is predominantly expressed in neuronal cells and plays an important role in neuronal migration, axon growth, fasciculation and lengthening in nervous system development [ 39 ]. When the phosphorylation of L1CAM protein is abnormal, the phosphorylation of PAK protein is hindered through the NRP1→Rac pathway, and the cells are hypoxic due to abnormal mitochondrial function and insufficient energy supply, which directly or indirectly activate autophagy and apoptosis-related proteins, such as P53 protein, AMPK protein, and mTOR protein, and induce apoptosis [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated network pharmacology and phosphoproteomic analyses of Baichanting in Parkinson's disease model mice

Gao,

Fu,

et al. 2024

Heliyon

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Clinical significance of L1CAM expression and its biological role in the progression of oral squamous cell carcinoma

Cited by 7 publications

References 40 publications

Cyclic increase in the ADAMTS1-L1CAM-EGFR axis promotes the EMT and cervical lymph node metastasis of oral squamous cell carcinoma

Cyclic increase in the ADAMTS1-L1CAM-EGFR axis promotes the EMT and cervical lymph node metastasis of oral squamous cell carcinoma

An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1

Integrated network pharmacology and phosphoproteomic analyses of Baichanting in Parkinson's disease model mice

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