A comparative study of slingshot homolog 1 (SSH1) and Lim kinase (LIMK) on mediating cancer radiosensitivity through regulation of cofilin-1

• Main Authors: Chun-Yu Wang, 王鈞右
• Other Authors: Yi-Jang Lee
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/5kj343

碩士 === 國立陽明大學 === 生物醫學影像暨放射科學系 === 105 === Radiotherapy is important for primary or adjuvant treatment of human cancers. To minimize the radiation damage on normal tissues, it is essential to develop and utilize radiosensitizers that can increase the efficacy of radiotherapy. We have previously found that latrunculin A (LA), an actin inhibitor could enhance radiosensitivity of cancer cells. Further, serine-3 phosphorylated cofilin-1, a member of actin depolymerizing factor (ADF)/cofilin family was dramatically increased by LA, but not total cofilin-1. Over-expression of constitutively phosphorylated cofilin-1 also enhanced cellular radiosensitivity. Because protein phosphotase slingshot homolog 1 (SSH1) and Rho-LIM kinase (LIMK) signaling can directly control the phosphorylated status of cofilin-1, it is of interest to investigate whether SSH1 and LIMK will also influence radiosensitivity. In this study, we found that LA would change the expression and activity of SSH1 but not LIMK. Knockdown of SSH1 also influenced the cellular radiosensitivity. Investigation of the LIMK-cofilin-1-SSH1 regulatory signaling circuit on radiosensitivity would be important for screening of appropriate radiosensitizers for cancer radiotherapy.