Open Access

Targeting CALR reduces energy metabolism of esophageal cancer cells and inhibits tumor‑associated fibroblast infiltration

  • Authors:
    • Yu Miao
    • Xiaofei Wang
    • Fang He
    • Feixiong Zhang
    • Ying Huang
    • Yafang Lai
    • Yuanzhen Wang
    • Lina Zhang
    • Hua Yin
    • Xiangkun Meng
    • Hao Liu
    • Weiqiang Li
    • Shaoqi Yang
  • View Affiliations

  • Published online on: May 19, 2025     https://doi.org/10.3892/ijo.2025.5755
  • Article Number: 49
  • Copyright: © Miao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Calreticulin (CALR) supports the induction of dendritic cell maturation, which makes it a key target for effective esophageal squamous cell carcinoma (ESCC) immunotherapy. The mechanism of CALR in the immunotherapy of ESCC is not fully studied. The aim of the present study was to explore the contributing role of CALR in ESCC progression. The association of CALR expression with calnexin (CANX) and protein disulfide isomerase A3 (PDIA3) expression in ESCC was analyzed. The functions of CALR in ESCC cells were examined by detection of cell migration, endoplasmic reticulum (ER) stress, mitochondrial function, cytoskeletal remodeling, cell proliferation and apoptosis. The effects of CALR on tumor growth and tumor‑associated fibroblast infiltration were examined by subcutaneous xenograft assay. The expression of CALR, CANX and PDIA3 in ESCC tissue significantly increased and the expression of PDIA3 was positively associated with CANX. Overexpression of CALR resulted in enhanced cell proliferation, migration, ER stress, mitochondrial function and cytoskeletal remodeling; knockdown of CALR expression had the opposite effect. In the subcutaneous xenograft assay, knockdown CALR significantly inhibited the growth of esophageal cancer tumors, suppressed the invasion of tumor‑associated fibroblasts and decreased the expression of α‑smooth muscle actin (α‑SMA), fibroblast activation protein (FAP), fibroblast specific protein‑1 (FSP1), platelet‑derived growth factor and transforming growth factor beta (TGF‑β) in tumor tissue. These findings suggested that CALR promotes the progression of ESCC by regulating ER stress and mitochondrial function to mediate ATP production, cytoskeletal remodeling, cell proliferation and apoptosis through CANX and PDIA3. Knockdown CALR significantly inhibited tumor‑associated fibroblast infiltration and is a potential drug target for ESCC.
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June-2025
Volume 66 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
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Spandidos Publications style
Miao Y, Wang X, He F, Zhang F, Huang Y, Lai Y, Wang Y, Zhang L, Yin H, Meng X, Meng X, et al: Targeting CALR reduces energy metabolism of esophageal cancer cells and inhibits tumor‑associated fibroblast infiltration. Int J Oncol 66: 49, 2025.
APA
Miao, Y., Wang, X., He, F., Zhang, F., Huang, Y., Lai, Y. ... Yang, S. (2025). Targeting CALR reduces energy metabolism of esophageal cancer cells and inhibits tumor‑associated fibroblast infiltration. International Journal of Oncology, 66, 49. https://doi.org/10.3892/ijo.2025.5755
MLA
Miao, Y., Wang, X., He, F., Zhang, F., Huang, Y., Lai, Y., Wang, Y., Zhang, L., Yin, H., Meng, X., Liu, H., Li, W., Yang, S."Targeting CALR reduces energy metabolism of esophageal cancer cells and inhibits tumor‑associated fibroblast infiltration". International Journal of Oncology 66.6 (2025): 49.
Chicago
Miao, Y., Wang, X., He, F., Zhang, F., Huang, Y., Lai, Y., Wang, Y., Zhang, L., Yin, H., Meng, X., Liu, H., Li, W., Yang, S."Targeting CALR reduces energy metabolism of esophageal cancer cells and inhibits tumor‑associated fibroblast infiltration". International Journal of Oncology 66, no. 6 (2025): 49. https://doi.org/10.3892/ijo.2025.5755