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.

No abstract

Overexpression of LIM and SH3 protein 1 (LASP1) is required for colorectal cancer (CRC) development and progression. Here, C-Jun activation domain-binding protein-1 (Jab1), also known as COP9 signalosome subunit 5 (COPS5), was verified as a new LASP1-interacting protein through yeast two-hybrid assay. The role of COPS5 in LASP1-mediated CRC progression remains unknown. GST pull-down assay indicated that the SH3 domain of LASP1 could directly bind to MPN domain of COPS5. In vitro gain- and loss-of-function analyses revealed the stimulatory role of COPS5 on CRC cell proliferation, migration and invasion. Endogenous overexpression of COPS5 could also enhance the homing capacity of CRC cells in vivo. Further analysis showed that COPS5 and LASP1 synergistically interact to stimulate the ubiquitination and degradation of 14-3-3σ and promote colorectal cancer progression via PI3K/Akt dependent signaling pathway. Clinically, the expression of COPS5 was studied in CRC tissues and it is associated with CRC differentiation, metastasis and poor prognosis. The colocalization of LASP1 and COPS5 was demonstrated in both nonmetastatic and metastatic CRC tissues. A positive correlation was found between the expression of LASP1 and COPS5 while a negative correlation existed between 14-3-3σ and COPS5/LASP1 in most CRC samples. A combination of COPS5 and LASP1 tends to be an independent prognostic indicator for CRC patients, and this is also suitable for CRC without lymph node metastasis. The current research has further advanced our understanding on the complicated molecular mechanism underlying LASP1-mediated CRC progression, which hopefully will contribute to the development of novel diagnostic and therapeutic strategies in CRC.