An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis

Cancer Letters
Man-Li LuoHai Hu

Abstract

Esophageal squamous cell carcinomas (ESCCs) have a poor prognosis mostly due to early metastasis. To explore the early event of metastasis in ESCC, we established an in vitro selection model to mimic the interaction of tumor cells with extracellular matrix, through which a sub-line of ESCC cells with high invasive ability was generated. By comparing the gene expression profile of the highly invasive sub-line to that of the parental cells, ADAM12-L was identified as a candidate gene promoting ESCC cell invasion. Immunohistochemistry revealed that the ADAM12-L was overexpressed in human ESCC tissues, especially at cancer invasive edge, and ADAM12-L overexpression tightly correlated with increased metastasis and poor outcome of ESCC patients. Indeed, ADAM12-L knockdown reduced the invasion and metastasis of ESCC cells both in vitro and in vivo. Furthermore, we demonstrated that ADAM12-L participated in focal adhesion turnover and promoted the activation of focal adhesion kinase (FAK), which in turn increased ADAM12-L transcription through FAK/JNK/c-Jun axis. Therefore, a loop initiated from the cancer cell upon the engagement with extracellular matrix through FAK and c-Jun to enhance ADAM12-L expression is established, leading to ...Continue Reading

Citations

Jan 8, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Xiangde ZhaoShuanglin Wan
Nov 6, 2018·Journal of Cellular Physiology·Yu MaoChao Wang
Aug 9, 2020·Cancer Management and Research·Peng HanFan Li
Feb 6, 2020·International Journal of Molecular Sciences·Saioa MendazaDavid Guerrero-Setas
May 7, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ru WangGregg L Semenza
Oct 1, 2021·European Journal of Histochemistry : EJH·Cuihong JiangQi Zhao

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