Overexpression of close homolog of L1 enhances the chemosensitivity of lung cancer cells via inhibition of the Akt pathway

Abstract

Drug resistance leads to tumor relapse and further progression during chemotherapy in lung cancer. Close homolog of L1 (CHL1) has been identified as a tumor suppressor in most malignancies. However, to the best of our knowledge, whether CHL1 mediates chemoresistance remains unknown. The present study observed that CHL1 was significantly downregulated in cisplatin (DDP)-resistant cells (A549/DDP) and paclitaxel (PTX)-resistant cells (A549/PTX) compared with A549 cells. When treated with or without DDP and PTX, silencing of CHL1 in A549 cells promoted the cell survival rate and clone formation, and decreased apoptosis. Whereas overexpression of CHL1 in A549/DDP and A549/PTX cells impeded the cell survival and clone formation and promoted apoptosis. Additionally, CHL1 overexpression enhanced the chemosensitivity of A549/DDP cells to DDP in vivo. Notably, the chemoresistance induced by CHL1 depletion was reversed by the Akt inhibitor SC66 in A549 cells. The results of the present study demonstrated that CHL1 enhanced sensitivity of lung cancer cells by suppressing the Akt pathway, which suggested that CHL1 may be a potential target for overcoming chemoresistance in lung cancer.

CHL1 inhibits cell proliferation, migration and invasion by regulating the NF‑κB signaling pathway in colorectal cancer

“…The cell adhesion molecule close homolog of L1 (CHL1) belongs to the cell adhesion molecule L1 (L1CAM) gene family ( 7 ), which is located at 3p26 and is involved in certain neurological diseases ( 8 ). Recently, CHL1 was defined to be involved in signal transduction pathways, as well as in the development of various human cancers, including breast cancer, CRC, bladder cancer and lung cancer ( 9 , 10 ). The downregulation of CHL1 expression has been observed in a variety of human tumors, including neuroblastoma, and breast and nasopharyngeal cancer ( 9 , 11 , 12 ).…”

Unveiling chemotherapy-induced immune landscape remodeling and metabolic reprogramming in lung adenocarcinoma by scRNA-sequencing

“…Chemotherapy drugs, however, are very toxic and are prone to invalid (3). In addition, continued ineffective chemotherapy will lead to the generation of drug-resistant tumor cell clones (4,5) and a delay in tumor removal. Almost all cancer patients show inherent or acquired drug resistance, leading to treatment failure and unsatisfactory overall survival.…”