LncRNA CamK-A Regulates Ca2+-Signaling-Mediated Tumor Microenvironment Remodeling. Academic Article uri icon

abstract

  • Cancer cells entail metabolic adaptation and microenvironmental remodeling to survive and progress. Both calcium (Ca2+) flux and Ca2+-dependent signaling play a crucial role in this process, although the underlying mechanism has yet to be elucidated. Through RNA screening, we identified one long noncoding RNA (lncRNA) named CamK-A (lncRNA for calcium-dependent kinase activation) in tumorigenesis. CamK-A is highly expressed in multiple human cancers and involved in cancer microenvironment remodeling via activation of Ca2+-triggered signaling. Mechanistically, CamK-A activates Ca2+/calmodulin-dependent kinase PNCK, which in turn phosphorylates IκBα and triggers calcium-dependent nuclear factor κB (NF-κB) activation. This regulation results in the tumor microenvironment remodeling, including macrophage recruitment, angiogenesis, and tumor progression. Notably, our human-patient-derived xenograft (PDX) model studies demonstrate that targeting CamK-A robustly impaired cancer development. Clinically, CamK-A expression coordinates with the activation of CaMK-NF-κB axis, and its high expression indicates poor patient survival rate, suggesting its role as a potential biomarker and therapeutic target.

published proceedings

  • Mol Cell

altmetric score

  • 0.75

author list (cited authors)

  • Sang, L., Ju, H., Liu, G., Tian, T., Ma, G., Lu, Y., ... Lin, A.

citation count

  • 68

complete list of authors

  • Sang, Ling-Jie||Ju, Huai-Qiang||Liu, Guang-Ping||Tian, Tian||Ma, Guo-Lin||Lu, Yun-Xin||Liu, Ze-Xian||Pan, Ruo-Lang||Li, Rui-Hua||Piao, Hai-Long||Marks, Jeffrey R||Yang, Luo-Jia||Yan, Qingfeng||Wang, Wenqi||Shao, Jianzhong||Zhou, Yubin||Zhou, Tianhua||Lin, Aifu

publication date

  • October 2018