2. Academic Validation
  3. Acetylation stabilizes stathmin1 and promotes its activity contributing to gallbladder cancer metastasis

Acetylation stabilizes stathmin1 and promotes its activity contributing to gallbladder cancer metastasis

  • Cell Death Discov. 2022 May 17;8(1):265. doi: 10.1038/s41420-022-01051-z.
Kun Fan  # 1 2 3 4 5,  Xiaojian Ni  # 1 3 4 5,  Sheng Shen  # 1 2 3 4 5,  Zijun Gong  # 1 3 4 5,  Jiwen Wang 1 3 4 5,  Yanlei Xin 1 3 4 5,  Bohao Zheng 1 3 4 5,  Wentao Sun 1 3 4 5,  Han Liu 1 3 4 5,  Tao Suo 1 3 4 5,  Xiaoling Ni 6 7 8 9,  Houbao Liu 10 11 12 13 14
Affiliations

Affiliations

  • 1 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 2 Department of General Surgery, Central Hospital of Xuhui District, Shanghai, China.
  • 3 Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, China.
  • 4 Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 5 Biliary Tract Disease Institute, Fudan University, Shanghai, China.
  • 6 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. ni.xiaoling@zs-hospital.sh.cn.
  • 7 Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, China. ni.xiaoling@zs-hospital.sh.cn.
  • 8 Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. ni.xiaoling@zs-hospital.sh.cn.
  • 9 Biliary Tract Disease Institute, Fudan University, Shanghai, China. ni.xiaoling@zs-hospital.sh.cn.
  • 10 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. liu.houbao@zs-hospital.sh.cn.
  • 11 Department of General Surgery, Central Hospital of Xuhui District, Shanghai, China. liu.houbao@zs-hospital.sh.cn.
  • 12 Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, China. liu.houbao@zs-hospital.sh.cn.
  • 13 Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. liu.houbao@zs-hospital.sh.cn.
  • 14 Biliary Tract Disease Institute, Fudan University, Shanghai, China. liu.houbao@zs-hospital.sh.cn.
  • # Contributed equally.
PMID: 35581193 DOI: 10.1038/s41420-022-01051-z
Abstract

Gallbladder Cancer is the most common biliary tract malignant tumor with highly metastatic characters and poor prognosis. However, the underlying mechanism remains unclear. Stathmin1 is ubiquitous phosphoprotein, regulating microtubule stabilization. We identified the acetylation of stahtmin1 at lysine 9 (K9) in gallbladder Cancer. K9 acetylation of stathmin1 was reversely regulated by the acetyltransferase PCAF and the deacetylases SIRT2. K9 acetylation of stathmin1 inhibited the combining of stathmin1 to E3 ubiquitin ligase RLIM, thereby inhibiting its ubiquitination degradation. Moreover, K9 acetylation also promoted the activity of stahtmin1 interacting and destabilizing microtubule through the inhibition of stathmin1 phosphorylation. K9 acetylated stathmin1 significantly promoted gallbladder Cancer cell migration and invasion viability in vitro and lung metastasis in vivo, and indicated poor prognosis of nude mice. IHC assay suggested the positive correlation of high levels of K9 acetylation and stathmin1 expression in gallbladder Cancer. Our study revealed that K9 acetylation up-regulated stathmin1 protein stability and microtubule-destabilizing activity to promoted gallbladder Cancer metastasis, which provides a potential target for gallbladder Cancer therapy.

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