2. Academic Validation
  3. MFAP3L activation promotes colorectal cancer cell invasion and metastasis

MFAP3L activation promotes colorectal cancer cell invasion and metastasis

  • Biochim Biophys Acta. 2014 Sep;1842(9):1423-32. doi: 10.1016/j.bbadis.2014.04.006.
Xiaomin Lou 1,  Bin Kang 1,  Jun Zhang 1,  Chunyi Hao 2,  Xiuyun Tian 2,  Wenmei Li 2,  Ningzhi Xu 3,  Youyong Lu 4,  Siqi Liu 5
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China.
  • 2 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing Institute for Cancer Research, 52 Fucheng Road, Haidian District, Beijing 100142, China.
  • 3 Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing 100021, China.
  • 4 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing Institute for Cancer Research, 52 Fucheng Road, Haidian District, Beijing 100142, China. Electronic address: yongylu@public.bta.net.cn.
  • 5 CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China. Electronic address: siqiliu@big.ac.cn.
PMID: 24735981 DOI: 10.1016/j.bbadis.2014.04.006
Abstract

An abundance of microfibril-associated glycoprotein 3-like (MFAP3L) significantly correlates with distant metastasis in colorectal Cancer (CRC), although the mechanism has yet to be explained. In this study, we observed that MFAP3L knock-down resulted in reduced CRC cell invasion and hepatic metastasis. We evaluated the cellular location and biochemical functions of MFAP3L and found that this protein was primarily localized in the nucleus of CRC cells and acted as a protein kinase. When EGFR translocated into the nucleus upon stimulation with EGF, MFAP3L was phosphorylated at Tyr287 within its SH2 motif, and the activated form of MFAP3L phosphorylated ERK2 at Thr185 and Tyr187. Moreover, the metastatic behavior of CRC cells in vitro and in vivo could be partially explained by activation of the nuclear ERK pathway through MFAP3L phosphorylation. Hence, we experimentally demonstrated for the first time that MFAP3L likely participates in the nuclear signaling of EGFR and ERK2 and acts as a novel nuclear kinase that impacts CRC metastasis.

Keywords

Colorectal cancer; MFAP3L; Metastasis; Protein kinase.

Figures