CDC73 suppresses migration, proliferation, and apoptosis resistance in esophageal squamous cell carcinoma via the JNK/p38/ERK MAPK pathway.
5 affiliations
- 1Department of Cardiovascular Surgery, Southeast University Affiliated Nantong First People's Hospital, Nantong, China.
- 2Department of Pathology, Medical School of Nantong University, Nantong, China.
- 3Department of Pharmacy, Nantong Second People's Hospital, Nantong, China.
- 4Department of Thoracic Surgery, Southeast University Affiliated Nantong First People's Hospital, Nantong, China.
- 5Department of Thoracic Surgery, Affiliated Nantong Clinical College of Nantong University, Nantong First People's Hospital, Nantong, China.
Abstract
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis, and the molecular regulators involved in its progression remain incompletely understood. This study aimed to evaluate the expression pattern and clinical significance of cell division cycle 73 (CDC73) in ESCC and to elucidate its regulatory role in malignant tumor cellular phenotypes. CDC73 expression levels in ESCC tissues and cell lines were systematically examined, and correlations with clinicopathological characteristics of patients were analyzed. Gain- and loss-of-function experiments were conducted to determine the effects of CDC73 on ESCC cell proliferation, migration, and apoptosis. Phosphorylation levels of key components of the mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), and extracellular signal-regulated kinase (ERK), were measured. The underlying molecular mechanisms were further validated through pathway inhibition assays. CDC73 expression was significantly downregulated in ESCC tissues and cell lines and was associated with unfavorable clinical characteristics. Functional analyses demonstrated that CDC73 overexpression significantly inhibited cellular proliferation and migration and increased apoptosis in ESCC cells. In contrast, CDC73 knockdown promoted proliferation and migration and suppressed apoptosis. Mechanistic analyses showed that CDC73 modulation was associated with altered MAPK signaling activity, characterized by reduced phosphorylation of ERK and p38 and increased phosphorylation of JNK following CDC73 overexpression, with the opposite pattern observed after CDC73 knockdown. These findings suggest that MAPK pathway remodeling may contribute to the phenotypic effects associated with CDC73 in ESCC. CDC73 may function as a tumor suppressor in ESCC by inhibiting cell proliferation and migration, promoting apoptosis, and modulating MAPK signaling activity. However, additional mechanistic studies, particularly rescue experiments, are required to determine whether these effects are directly mediated by PAF1C-dependent transcriptional regulation and to establish the causal relationship between CDC73 and the observed malignant phenotypes.
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BibTeX
@article{li2026cdc73,
title = {{CDC73 suppresses migration, proliferation, and apoptosis resistance in esophageal squamous cell carcinoma via the JNK/p38/ERK MAPK pathway.}},
author = {Yan Li and Rui Chen and Xiaomin Guan and Liang Shen},
journal = {Journal of gastrointestinal oncology},
year = {2026},
month = aug,
doi = {10.21037/jgo-2026-0443},
url = {https://europepmc.org/article/MED/42996619},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - CDC73 suppresses migration, proliferation, and apoptosis resistance in esophageal squamous cell carcinoma via the JNK/p38/ERK MAPK pathway.
AU - Yan Li
AU - Rui Chen
AU - Xiaomin Guan
AU - Liang Shen
PY - 2026
DA - 2026/08/13
JO - Journal of gastrointestinal oncology
DO - 10.21037/jgo-2026-0443
UR - https://europepmc.org/article/MED/42996619
AB - Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis, and the molecular regulators involved in its progression remain incompletely understood. This study aimed to evaluate the expression pattern and clinical significance of cell division cycle 73 (CDC73) in ESCC and to elucidate its regulatory role in malignant tumor cellular phenotypes. CDC73 expression levels in ESCC tissues and cell lines were systematically examined, and correlations with clinicopathological characteristics of patients were analyzed. Gain- and loss-of-function experiments were conducted to determine the effects of CDC73 on ESCC cell proliferation, migration, and apoptosis. Phosphorylation levels of key components of the mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), and extracellular signal-regulated kinase (ERK), were measured. The underlying molecular mechanisms were further validated through pathway inhibition assays. CDC73 expression was significantly downregulated in ESCC tissues and cell lines and was associated with unfavorable clinical characteristics. Functional analyses demonstrated that CDC73 overexpression significantly inhibited cellular proliferation and migration and increased apoptosis in ESCC cells. In contrast, CDC73 knockdown promoted proliferation and migration and suppressed apoptosis. Mechanistic analyses showed that CDC73 modulation was associated with altered MAPK signaling activity, characterized by reduced phosphorylation of ERK and p38 and increased phosphorylation of JNK following CDC73 overexpression, with the opposite pattern observed after CDC73 knockdown. These findings suggest that MAPK pathway remodeling may contribute to the phenotypic effects associated with CDC73 in ESCC. CDC73 may function as a tumor suppressor in ESCC by inhibiting cell proliferation and migration, promoting apoptosis, and modulating MAPK signaling activity. However, additional mechanistic studies, particularly rescue experiments, are required to determine whether these effects are directly mediated by PAF1C-dependent transcriptional regulation and to establish the causal relationship between CDC73 and the observed malignant phenotypes.
SN - 2078-6891
SN - 2219-679X
ER -