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CACNA2D1 regulates the progression and influences the microenvironment of colon cancer.
Inoue, Hiroyuki; Shiozaki, Atsushi; Kosuga, Toshiyuki; Shimizu, Hiroki; Kudou, Michihiro; Arita, Tomohiro; Konishi, Hirotaka; Komatsu, Shuhei; Kuriu, Yoshiaki; Kubota, Takeshi; Fujiwara, Hitoshi; Morinaga, Yukiko; Konishi, Eiichi; Otsuji, Eigo.
Affiliation
  • Inoue H; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Shiozaki A; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan. shiozaki@koto.kpu-m.ac.jp.
  • Kosuga T; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Shimizu H; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Kudou M; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Arita T; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Konishi H; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Komatsu S; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Kuriu Y; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Kubota T; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Fujiwara H; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
  • Morinaga Y; Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Konishi E; Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Otsuji E; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, 602-8566, Japan.
J Gastroenterol ; 59(7): 556-571, 2024 Jul.
Article in En | MEDLINE | ID: mdl-38536483
ABSTRACT

BACKGROUND:

Calcium voltage-gated channel auxiliary subunit alpha 2/delta 1 (CACNA2D1), a gene encoding a voltage-gated calcium channel, has been reported as an oncogene in several cancers. However, its role in colon cancer (CC) remains unclear. This study aimed to investigate the function of CACNA2D1 and its effect on the microenvironment in CC.

METHODS:

Immunohistochemistry (IHC) analysis was performed on samples collected from 200 patients with CC who underwent curative colectomy. Knockdown experiments were performed using CACNA2D1 siRNA in the human CC cell lines HCT116 and RKO, and cell proliferation, cycle, apoptosis, and migration were then analyzed. The fibroblast cell line CCD-18Co was co-cultured with CC cell lines to determine the effect of CACNA2D1 on fibroblasts and the relationship between CACNA2D1 and the cancer microenvironment. Gene expression profiles of cells were analyzed using microarray analysis.

RESULTS:

IHC revealed that high CACNA2D1 expression was an independent poor prognostic factor in patients with CC and that CACNA2D1 expression and the stroma are correlated. CACNA2D1 depletion decreased cell proliferation and migration; CACNA2D1 knockdown increased the number of cells in the sub-G1 phase and induced apoptosis. CCD-18Co and HCT116 or RKO cell co-culture revealed that CACNA2D1 affects the cancer microenvironment via fibroblast regulation. Furthermore, microarray analysis showed that the p53 signaling pathway and epithelial-mesenchymal transition-associated pathways were enhanced in CACNA2D1-depleted HCT116 cells.

CONCLUSIONS:

CACNA2D1 plays an important role in the progression and the microenvironment of CC by regulating fibroblasts and may act as a biomarker for disease progression and a therapeutic target for CC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium Channels / Apoptosis / Colonic Neoplasms / Disease Progression / Tumor Microenvironment Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: J Gastroenterol Journal subject: GASTROENTEROLOGIA Year: 2024 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium Channels / Apoptosis / Colonic Neoplasms / Disease Progression / Tumor Microenvironment Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: J Gastroenterol Journal subject: GASTROENTEROLOGIA Year: 2024 Document type: Article Affiliation country: Country of publication: