CKAP2L Promotes Esophageal Squamous Cell Carcinoma Progression and Drug-Resistance by Modulating Cell Cycle

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer and the leading cause of cancer-related mortality worldwide, especially in Asia. In this study, the gene CKAP2L was selected by GEO, TCGA, and GTEx database analysis. The high expression of CKAP2L is related to the occurrence and development of ESCC. In addition, CKAP2L knockdown can inhibit the growth and migration of ESCC cells, while CKAP2L overexpression has the opposite effect. Furthermore, in vivo experiments indicated that down-regulation of CKAP2L can inhibit the tumorigenesis of ESCC cells. KEGG pathway analysis and the STRING database explored the relationship between cell cycle and CKAP2L and verified that depletion of CKAP2L markedly arrested cell cycle in the G2/M phase. Meanwhile, CKAP2L knockdown increased the sensitivity of ESCC cells to flavopiridol, the first CDK inhibitor to be tested in clinical trials, leading to an observable reduction in cell proliferation and an increase in cellular apoptosis. In brief, we identified CKAP2L as a tumor promoter, potential prognostic indicator, and therapeutic target of ESCC, which may play a role in regulating cell cycle progression.

Pan-cancer analysis reveals the prognostic and immunotherapeutic value of cytoskeleton-associated protein 2-like

“…Flow cytometry results showed that knockdown of CKAP2L resulted in cell cycle G2/M arrest. Similar to previous studies 5 – 7 , we suggested that CKAP2L may contribute to tumor progression in KIRC by influencing the biological behavior of cancer cells through the cell cycle too. However, we only validated the effect of CKAP2L in KIRC and further studies are needed to assess the role of CKAP2L in the other tumors.…”

“…CKAP2L is a mitotic spindle protein that has been previously shown to be overexpressed in some tumors and to be associated with tumor progression and patient prognosis. In prostate cancer, esophageal squamous cell carcinoma and glioblastoma, CKAP2L has been shown to affect the biological behavior of cancer cells by regulating the cell cycle 5 – 7 . A breast cancer study has shown that CKAP2L activates the AKT/mTOR signaling pathway and thus promotes breast cancer development 9 .…”

“…It has been suggested that loss-of-function mutations in this gene are the main cause of Filippi's syndrome 4 . So far, CKAP2L has only been studied in a few types of tumors and has been shown to be highly expressed and to promote tumor progression in prostate cancer 5 , glioblastoma 6 , oesophageal squamous cell carcinoma 7 , non-small cell lung cancer 8 and breast cancer 9 , where it is a potential prognostic biomarker. However, no studies have yet explored CKAP2L at the pan-cancer level.…”