Chordin-Like 1 Regulates Epithelial-to-Mesenchymal Transition and Metastasis via the MAPK Signaling Pathway in Oral Squamous Cell Carcinoma.

ABSTRACT

Background: Accumulating evidence suggests that dysregulation of Chordin-like 1 (CHRDL1) is associated with malignant biological behaviors in multiple cancers. However, the exact function and molecular mechanism of CHRDL1 in oral squamous cell carcinoma (OSCC) remain unclear. Methods: The expression levels of CHRDL1 in OSCC tissues and CAL27 cells were determined by RT-qPCR. Immunohistochemical staining was applied to detect CHRDL1 protein expression in sample tissues from OSCC patients. Gain of function and knockdown by lentivirus were further used to examine the effects of CHRDL1 on cell proliferation, migration, invasion, and adhesion in OSCC. Tail vein injection of CAL27 cells with dysregulated CHRDL1 expression was further used to examine the effect of CHRDL1 on lung colonization. RNA sequencing was performed to explore the molecular mechanisms of CHRDL1 that underlie the progression of OSCC. Results: CHRDL1 was significantly downregulated in OSCC tissues and CAL27 cells compared to controls. CHRDL1 knockdown enhanced migration, invasion, adhesion, and EMT, but not proliferation, in CAL27 cells. Overexpression of CHRDL1 had the opposite effects. Moreover, CHRDL1 was proven to inhibit tumor metastasis in vivo. Mechanistically, MAPK signaling pathway components, including ERK1/2, p38, and JNK, were found to regulate the malignant biological behaviors of CAL27 cells. Conclusions: Our results suggest that CHRDL1 has an inhibitory effect on OSCC metastasis via the MAPK signaling pathway, which provides a new possible potential therapeutic target against OSCC.