Lysosomal-Associated Transmembrane Protein 5 Promotes Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most aggressive and deadly cancer of the urinary system and is regulated by multiple signaling pathways. However, the specific molecular mechanisms underlying ccRCC have not been fully studied or demonstrated. This study aimed to elucidate the function of lysosomal-associated transmembrane protein 5 (LAPTM5) in ccRCC cell lines and animal models and determine the potential underlying mechanisms. Our results demonstrated that LAPTM5 expression in patients with ccRCC was significantly higher in the tumor group than that in the adjacent nontumor group. Moreover, LAPTM5 promoted proliferation, migration, and invasion of ccRCC cells through the gain and loss of the function of LAPTM5 in 786-0 and Caki-1 cell lines. Similar results regarding LAPTM5 overexpression were obtained in BALB/c nude mice. In addition, LAPTM5 activated the Jun N-terminal kinase (JNK)/p38 signaling cascade by interacting with Ras-related C3 botulinum toxin substrate 1 (RAC1). Treatment with an RAC1 inhibitor eliminated the effects of LAPTM5 in ccRCC. In conclusion, these results indicate that LAPTM5 may be a new therapeutic target for ccRCC via activation of the RAC1-JNK/p38 axis.

HIF-1α/LAPTM5/STAT1 axis promotes the malignant progression of clear cell renal cell carcinoma

“…Moreover, LAPTM5 also functions as a tumour suppressor in several types of cancer, such as oestrogen receptor-positive breast cancer and neuroblastoma 13,14 . In ccRCC, LAPTM5 functions as an oncogene and promotes cell proliferation, migration, and invasion by activating the RAC1-JNK/p38 axis 15 .…”