Mechanism Of Lis1 In Promoting Perineural Invasion Of Hnscc

This study investigates the role of LIS1 in promoting perineural invasion (PNI) and metastasis in HNSCC. LIS1 expression was assessed in HNSCC using TCGA datasets. To evaluate the correlation between LIS1 and PNI in vivo and in vitro, we performed H&E and IHC staining on pathological sections, and established a SCC25-Schwann cells (SCs) co-culture system. Next, bioinformatics analysis was conducted to identify LIS1-related pathways and differentially expressed genes, then RT-qPCR and Western blot was used to validate these findings. For the PNI model in vivo, we selected three-week-old BALB/C nude mice, randomly divided them into four groups, and dissected tumors after 7 weeks to detect the relationship of LIS1 and PNI in HNSCC. In HNSCC, LIS1 was significantly upregulated and positively correlated with S100/ GDNF(markers of SCs); high expression of LIS1 in SCC25 promoted SCs migration and invasion. Compared to the control group, LIS1 was closely associated with the serine metabolic pathway, and the mRNA and protein expression of three key rate-limiting enzymes of serine metabolism were downregulated in the shLIS1 group. In vivo, HE staining indicated that the tumor cells were closest to the nerve in the LIS1 group, and IHC staining showed that the expression of neuroinvasion-related factors, PHGDH, and the serine receptor NMDAR1 were significantly upregulated compared to the control groups. LIS1 mediated SCs reprogramming facilitates PNI in HNSCC by activating the Serine/NMDAR signaling pathway.