2. Academic Validation
  3. RACK1 promotes the invasive activities and lymph node metastasis of cervical cancer via galectin-1

RACK1 promotes the invasive activities and lymph node metastasis of cervical cancer via galectin-1

  • Cancer Lett. 2020 Jan 28;469:287-300. doi: 10.1016/j.canlet.2019.11.002.
Hao Wu 1,  Shushu Song 1,  Anqi Yan 2,  Xinying Guo 1,  Lei Chang 3,  Ling Xu 1,  Lan Hu 1,  Mengzhen Kuang 1,  Bo Liu 1,  Daochuan He 1,  Ran Zhao 2,  Lan Wang 4,  Xin Wu 5,  Jianxin Gu 1,  Yuanyuan Ruan 6
Affiliations

Affiliations

  • 1 Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, PR China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China.
  • 2 Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, PR China.
  • 3 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, PR China.
  • 4 Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, PR China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China. Electronic address: lanwang10@fudan.edu.cn.
  • 5 Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, PR China. Electronic address: sky_xin1980@aliyun.com.
  • 6 Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, PR China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China. Electronic address: yuanyuanruan@fudan.edu.cn.
PMID: 31705928 DOI: 10.1016/j.canlet.2019.11.002
Abstract

Cervical Cancer remains the first leading cause of cancer-related mortality among female reproductive system malignancies worldwide, and invasion and lymph node metastasis of cervical Cancer represent the major reason for its poor prognosis. In this study, we found that RACK1 facilitated tumor cell invasion and lymphatic tube formation in vitro, as well as promoted lymphangiogenesis and lymph node metastasis in vivo in a galectin-1-dependent manner. Mechanism studies revealed that RACK1 promoted the expression and secretion of Galectin-1 by reducing miR-1275 levels. Additionally, RACK1 also augmented galectin-1-induced downstream MEK/ERK, FAK, and Akt signaling via integrin-β1 in cervical Cancer cells. Tissue microarray confirmed that RACK1 was upregulated in squamous intraepithelial lesion and Cancer, and RACK1 was positively correlated with invasion/metastasis phenotype, Galectin-1 expression, and unfavorable prognosis in cervical Cancer cases. Human papillomavirus E6 oncogene contributes to increased expression of RACK1 via the enhancement of its O-GlcNAcylation and protein stability. Together, our results demonstrate that RACK1 stimulates tumor invasion and lymph node metastasis of cervical Cancer via Galectin-1 and imply that targeting RACK1/Galectin-1 axis provides promising means for cervical Cancer treatment.

Keywords

Human papillomavirus; Integrin-β1; Lymphangiogenesis; O-GlcNAcylation; miRNA-1275.

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