Journal
MOLECULAR CELL
Volume 72, Issue 1, Pages 71-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2018.08.014
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Funding
- National Natural Science Foundation of China [91740205, 81672791, 81872300, 81602137, 31571299, 31771398]
- Stem Cell and Translational Research
- National Key Research and Development Program of China [2016YFA0101001]
- Zhejiang Provincial Natural Science Fund for Distinguished Young Scholars of China [LR18C060002]
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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 I kappa B alpha and triggers calcium-dependent nuclear factor KB (NF-kappa B) 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-kappa B axis, and its high expression indicates poor patient survival rate, suggesting its role as a potential biomarker and therapeutic target.
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