CACNA2D1, encoding the α2δ-1 protein, is a gene for an auxiliary subunit of voltage-gated calcium channels. These channels are crucial for calcium ion influx, which is involved in numerous cellular processes such as corticogenesis, transcription, and synaptogenesis [4]. The α2δ subunits play important roles in the trafficking and function of the CaV channel complexes [2].

Functional studies have shown that biallelic loss-of-function variants in CACNA2D1 underlie severe neurodevelopmental disorder, like early-onset developmental epileptic encephalopathy [2]. In cancer research, knockdown of CACNA2D1 in colon cancer cell lines decreased cell proliferation and migration, increased apoptosis, and affected the cancer microenvironment via fibroblast regulation [1]. In gastric cancer cell lines, CACNA2D1-depleted cells also showed suppressed proliferation, migration, and invasion, along with induced apoptosis, and the apoptosis signaling pathway was enhanced via p53, BAX, and caspase 3 [3]. In breast cancer, CACNA2D1 might be beneficial as it could improve the prognosis by increasing immune cells infiltrating into the cancer and up-regulating immune checkpoint expression [5].

In conclusion, CACNA2D1 is essential for the normal function of voltage-gated calcium channels and normal human neuronal development. Its role in cancer, especially in colon, gastric, and breast cancer, has been demonstrated through functional studies including knockdown experiments, highlighting its potential as a biomarker and therapeutic target in these diseases.

References:

1. Inoue, Hiroyuki, Shiozaki, Atsushi, Kosuga, Toshiyuki, Konishi, Eiichi, Otsuji, Eigo. 2024. CACNA2D1 regulates the progression and influences the microenvironment of colon cancer. In Journal of gastroenterology, 59, 556-571. doi:10.1007/s00535-024-02095-x. https://pubmed.ncbi.nlm.nih.gov/38536483/

2. Dahimene, Shehrazade, von Elsner, Leonie, Holling, Tess, Kutsche, Kerstin, Dolphin, Annette C. . Biallelic CACNA2D1 loss-of-function variants cause early-onset developmental epileptic encephalopathy. In Brain : a journal of neurology, 145, 2721-2729. doi:10.1093/brain/awac081. https://pubmed.ncbi.nlm.nih.gov/35293990/

3. Inoue, Hiroyuki, Shiozaki, Atsushi, Kosuga, Toshiyuki, Konishi, Eiichi, Otsuji, Eigo. 2022. Functions and Clinical Significance of CACNA2D1 in Gastric Cancer. In Annals of surgical oncology, , . doi:10.1245/s10434-022-11752-5. https://pubmed.ncbi.nlm.nih.gov/35445337/

4. Kessi, Miriam, Chen, Baiyu, Peng, Jing, Yang, Lifen, Yin, Fei. 2021. Calcium channelopathies and intellectual disability: a systematic review. In Orphanet journal of rare diseases, 16, 219. doi:10.1186/s13023-021-01850-0. https://pubmed.ncbi.nlm.nih.gov/33985586/

5. Liang, Jiamin, Deng, Yu, Zhang, Yubi, Wu, Bin, Zhou, Jing. 2022. PRLR and CACNA2D1 Impact the Prognosis of Breast Cancer by Regulating Tumor Immunity. In Journal of personalized medicine, 12, . doi:10.3390/jpm12122086. https://pubmed.ncbi.nlm.nih.gov/36556307/