TY  - JOUR
A1  - Subramaniyan, Boopathi
A1  - Sridharan, Sangita
A1  - Howard, Cory M.
A1  - Tilley, Augustus M.C.
A1  - Basuroy, Tupa
A1  - Serna, Ivana de la
A1  - Butt, Elke
A1  - Raman, Dayanidhi
T1  - Role of the CXCR4-LASP1 axis in the stabilization of Snail1 in triple-negative breast cancer
JF  - Cancers
N2  - The CXCL12-CXCR4 axis plays a vital role in many steps of breast cancer metastasis, but the molecular mechanisms have not been fully elucidated. We previously reported that activation of CXCR4 by CXCL12 promotes the nuclear localization of LASP1 (LIM and SH3 protein 1). The nuclear LASP1 then interacts with Snail1 in triple-negative breast cancer (TNBC) cell lines. In this study, we report that the nuclear accumulation and retention of Snail1 was dependent on an increase in nuclear LASP1 levels driven by active CXCR4. The CXCR4-LASP1 axis may directly regulate the stabilization of nuclear Snail1, by upregulating nuclear levels of pS473-Akt, pS9-GSK-3β, A20, and LSD1. Furthermore, the activation of CXCR4 induced association of LASP1 with Snail1, A20, GSK-3β, and LSD1 endogenously. Thus, nuclear LASP1 may also regulate protein-protein interactions that facilitate the stability of Snail1. Genetic ablation of LASP1 resulted in the mislocalization of nuclear Snail1, loss of the ability of TNBC cells to invade Matrigel and a dysregulated expression of both epithelial and mesenchymal markers, including an increased expression of ALDH1A1, a marker for epithelial breast cancer stem-like cells. Our findings reveal a novel role for the CXCR4-LASP1 axis in facilitating the stability of nuclear localized Snail1.
KW  - CXCR4
KW  - LASP1
KW  - Akt
KW  - Snail1 stability
KW  - A20
KW  - GSK-3β
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211217
SN  - 2072-6694
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Butt, Elke
A1  - Howard, Cory M.
A1  - Raman, Dayanidhi
T1  - LASP1 in cellular signaling and gene expression: more than just a cytoskeletal regulator
JF  - Cells
N2  - LIM and SH3 protein 1 was originally identified as a structural cytoskeletal protein with scaffolding function. However, recent data suggest additional roles in cell signaling and gene expression, especially in tumor cells. These novel functions are primarily regulated by the site-specific phosphorylation of LASP1. This review will focus on specific phosphorylation-dependent interaction between LASP1 and cellular proteins that orchestrate primary tumor progression and metastasis. More specifically, we will describe the role of LASP1 in chemokine receptor, and PI3K/AKT signaling. We outline the nuclear role for LASP1 in terms of epigenetics and transcriptional regulation and modulation of oncogenic mRNA translation. Finally, newly identified roles for the cytoskeletal function of LASP1 next to its known canonical F-actin binding properties are included.
KW  - LASP1
KW  - AKT
KW  - CXCR4
KW  - structure
KW  - cytoskeleton
KW  - phosphorylation
KW  - transcriptional regulation
KW  - epigenetics
KW  - nucleus
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297447
SN  - 2073-4409
VL  - 11
IS  - 23
ER  -