2. Academic Validation
  3. Mutations and clinical significance of calcium voltage-gated channel subunit alpha 1E (CACNA1E) in non-small cell lung cancer

Mutations and clinical significance of calcium voltage-gated channel subunit alpha 1E (CACNA1E) in non-small cell lung cancer

  • Cell Calcium. 2022 Mar:102:102527. doi: 10.1016/j.ceca.2022.102527.
San-Hui Gao 1,  Gui-Zhen Wang 2,  Li-Peng Wang 3,  Lin Feng 4,  Yong-Chun Zhou 5,  Xian-Jun Yu 6,  Fan Liang 1,  Fu-Ying Yang 7,  Zheng Wang 7,  Bei-Bei Sun 7,  Di Wang 7,  Li-Jun Liang 7,  Da-Wei Xie 7,  Song Zhao 6,  Hai-Ping Feng 6,  Xueqing Li 8,  Keqin Kathy Li 8,  Tie-Shan Tang 6,  Yun-Chao Huang 5,  Shi-Qiang Wang 3,  Guang-Biao Zhou 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing, 100101, China; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 2 State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address: [email protected].
  • 3 State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, 100091, China.
  • 4 Department of Pathology, Chinese PLA General Hospital, Beijing, 100853, China.
  • 5 Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming, 650106, China.
  • 6 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing, 100101, China.
  • 7 State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 8 Computer Science Department, University of North Georgia, Dahlonega, GA, 30597, United States.
  • 9 State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address: [email protected].
PMID: 35026540 DOI: 10.1016/j.ceca.2022.102527
Abstract

CACNA1E is a gene encoding the ion-conducting α1 subunit of R-type voltage-dependent calcium channels, whose roles in tumorigenesis remain to be determined. We previously showed that CACNA1E was significantly mutated in patients with non-small cell lung Cancer (NSCLC) who were long-term exposed to household air pollution, with a mutation rate of 19% (15 of 79 cases). Here we showed that CACNA1E was also mutated in 207 (12.8%) of the 1616 patients with NSCLC in The Cancer Genome Atlas (TCGA) datasets. At mRNA and protein levels, CACNA1E was elevated in tumor tissues compared to counterpart non-tumoral lung tissues in NSCLCs of the public datasets and our settings, and its expression level was inversely associated with clinical outcome of the patients. Overexpression of wild type (WT) or A275S or R249G mutant CACNA1E transcripts promoted NSCLC cell proliferation with activation of epidermal growth factor receptor (EGFR) signaling pathway, whereas knockdown of this gene exerted inhibitory effects on NSCLC cells in vitro and in vivo. CACNA1E increased current density and CA2+ entrance, whereas Calcium Channel blockers inhibited NSCLC cell proliferation. These data indicate that CACNA1E is required for NSCLC cell proliferation, and blockade of this oncoprotein may have therapeutic potentials for this deadly disease.

Keywords

CACNA1E; Cell proliferation; EGFR; Intracellular calcium concentration; Non-small cell lung cancer.

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