L1CAM enhances autophagy via inhibition of p38 phosphorylation in colorectal cancer development and progression

Colorectal cancer (CRC) is a common gastrointestinal tumor with a high incidence worldwide. L1 cell adhesion molecule (L1CAM) is highly expressed in CRC tissues and can promote tumor growth and metastasis. Autophagy regulates oncogenesis and tumor progression through context-dependent mechanisms and is regulated by multiple signaling pathways, including the p38 MAPK signaling pathway.

However, the relationship between L1CAM and autophagy is not known yet. In this study, we are trying to dissect the role of L1CAM-autophagy interaction in the development and progression of CRC and its underlying mechanism.

Stable L1CAM knockdown was achieved in SW480 and HT29 cells via lentiviral transduction of specific shRNAs. Autophagic flux was detected using western blotting and Tandem mRFP-GFP-LC3 assay. The protein levels were measured via western blotting. Cell proliferation was tested via CCK-8 proliferation assay and Edu staining. Apoptosis was evaluated using flow cytometry.

We found that upon L1CAM knockdown, the phosphorylation of p38 was enhanced, and autophagy was weakened. When p38 phosphorylation was inhibited, the inhibitory effect of L1CAM knockdown on autophagy was restored. And L1CAM can promote cell proliferation and inhibit cell apoptosis.

Taken together, these findings indicate that L1CAM promotes autophagy by inhibiting the phosphorylation of p38, and that it also promotes cell proliferation and inhibits cell apoptosis in colon cancer cells. L1CAM might be as a new target in CRC therapy.