LASP1 promotes nasopharyngeal carcinoma progression through negatively regulation of the tumor suppressor PTEN

• Published in: Cell death & disease Vol. 9; no. 3; pp. 393 - 11
• Main Authors: Gao, Qingzu, Tang, Lihua, Wu, Ling, Li, Kaitao, Wang, Hui, Li, Weidong, Wu, Juan, Li, Mingyi, Wang, Shuang, Zhao, Liang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.03.2018; Springer Nature B.V
• Subjects: 13/109; 13/89; 13/95; 14/1; 14/63; 64/60; 82/29; 82/51; AKT protein; Antibodies; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell growth; Cell migration; Cell proliferation; Immunology; Invasiveness; Kinases; Life Sciences; Localization; Metastases; Metastasis; Nasopharyngeal carcinoma; Phosphorylation; PTEN protein; Signal transduction; Therapeutic applications; Throat cancer; Tumor suppressor genes; Ubiquitination
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-0443-y

LIM and SH3 protein 1 (LASP1) enhances tumor growth and metastasis in various cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. Herein, we investigated the role of LASP1 in NPC and explored the underlying mechanisms in NPC. Clinically, overexpression of LASP1 is associated with tumor metastasis and poor prognosis of NPC patients. Gain-of-function and loss-of-function assays showed that LASP1 promoted NPC cell proliferation, metastasis, and invasion in vitro and in vivo. Mechanistically, we observed clear co-localization between LASP1 and PTEN in NPC cells. LASP1 interacted with PTEN and decreased the expression of PTEN in NPC. The ubiquitination assay indicated that LASP1 overexpression increased PTEN ubiquitination. PTEN was known as a tumor suppressor by negatively regulating phosphoinositide 3-kinase/AKT signaling pathway. Rescue experiments showed that PTEN weakened LASP1-mediated cell proliferation, migration, and invasive abilities and decreased the phosphorylation of AKT in NPC cells. Our findings suggest that LASP1 has a crucial role in NPC progression via LASP1/PTEN/AKT axis, highlighting LASP1 as a therapeutic target for NPC.