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

Ruo-Hui Huang; Zi-Lu Ge; Gang Xu; Qing-Ming Zeng; Wei Xia; Guan-Cheng Xiao; Xiao-Feng Zou; Bin-Bin Zhang

doi:10.1155/2022/6334546

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

J Oncol. 2022 Nov 2:2022:6334546. doi: 10.1155/2022/6334546. eCollection 2022.

Authors

Ruo-Hui Huang^{1

2

3}, Zi-Lu Ge⁴, Gang Xu^{2

3}, Qing-Ming Zeng^{2

3}, Wei Xia^{2

3}, Guan-Cheng Xiao^{2

3}, Xiao-Feng Zou^{2

3}, Bin-Bin Zhang⁵

Affiliations

¹ Medical College of Soochow University, Suzhou, Jiangsu 215006, China.
² Department of Urology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiang Xi 341000, China.
³ Jiangxi Stone Prevention Engineering Technology Research Center, Ganzhou, Jiang Xi 341000, China.
⁴ First Clinical Medical College, Gannan Medical University, Ganzhou, Jiang Xi 341000, China.
⁵ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan 450052, China.

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.