Sato Misaki, Yoneyama Mihoko Sutoh, Hatakeyama Shingo, Funyu Tomihisa, Suzuki Tadashi, Ohyama Chikara, Tsuboi Shigeru
Department of Cancer Immunology and Cell Biology, Oyokyo Kidney Research Institute, Hirosaki, Aomori 036-8243, Japan.
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan.
Oncol Lett. 2017 Oct;14(4):4829-4834. doi: 10.3892/ol.2017.6802. Epub 2017 Aug 23.
The LIM and SH3 protein-1 (LASP-1) is a multi-domain protein that is involved in several malignant cancers. The role of LASP-1 in malignant phenotypes including high invasive properties and unrestricted cell proliferation, remain to be elucidated. The present study reported the association of LASP-1 expression with bladder cancer malignancy and its role in cancer cell invasion and proliferation. The immunohistochemical analysis of the expression status of LASP-1 in radical cystectomy specimens from invasive bladder cancer patients revealed that the LASP-1-positive patients demonstrated a decreased survival rate compared with the LASP-1-negative patients. The expression level of LASP-1 was increased in invasive bladder cancer cell lines compared with the non-invasive bladder cancer cell lines. Invasive cancer cells form invadopodia, the filamentous actin-based membrane protrusions that are essential in cancer cell invasion. Knockdown of LASP-1 reduced the ability to form invadopodia, resulting in decreased invasive capacity of the LASP-1 knockdown cells. In addition, knockdown of LASP-1 reduced cell proliferation. These results suggest that LASP-1 is important in invadopodia formation and cell proliferation of bladder cancer cells, promoting the malignant properties and resulting in poor-prognosis.
LIM和SH3结构域蛋白-1（LASP-1）是一种多结构域蛋白，与多种恶性肿瘤有关。LASP-1在包括高侵袭性和不受限制的细胞增殖等恶性表型中的作用仍有待阐明。本研究报道了LASP-1表达与膀胱癌恶性程度的关联及其在癌细胞侵袭和增殖中的作用。对浸润性膀胱癌患者根治性膀胱切除标本中LASP-1表达状态的免疫组化分析显示，与LASP-1阴性患者相比，LASP-1阳性患者的生存率降低。与非浸润性膀胱癌细胞系相比，浸润性膀胱癌细胞系中LASP-1的表达水平升高。浸润性癌细胞形成侵袭伪足，这是基于丝状肌动蛋白的膜突起，对癌细胞侵袭至关重要。敲低LASP-1可降低形成侵袭伪足的能力，导致LASP-1敲低细胞的侵袭能力下降。此外，敲低LASP-1可减少细胞增殖。这些结果表明，LASP-1在膀胱癌细胞的侵袭伪足形成和细胞增殖中起重要作用，促进恶性特性并导致预后不良。
