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CLCA2 的过表达通过抑制 ERK/JNK/p38-MAPK 信号通路抑制宫颈癌细胞的上皮间质转化。

CLCA2 overexpression suppresses epithelial-to-mesenchymal transition in cervical cancer cells through inactivation of ERK/JNK/p38-MAPK signaling pathways.

机构信息

Department of Gynecology, Lanzhou University Second Hospital, Lanzhou, 730030, China.

The Second Clinical Medical College of Lanzhou University, Lanzhou, 730000, China.

出版信息

BMC Mol Cell Biol. 2022 Oct 25;23(1):44. doi: 10.1186/s12860-022-00440-7.

DOI:10.1186/s12860-022-00440-7
PMID:36280802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9594891/
Abstract

Cervical cancer is an important malignant tumor threatening the physical and mental health of women in the world. As a new calcium activated chloride channel protein, calcium activated chloride channel (CLCA2) plays an important role in tumorigenesis and development. But its role and exact regulatory mechanism in cervical cancer are still unclear. In our study, we found CLCA2 was significantly decreased in cervical cancer cells, and overexpression of CLCA2 inhibited the proliferation, migration and invasion, and promotes apoptosis of cervical cancer cells, and CLCA2 inhibited EMT (Epithelial-mesenchymal transition) through an p38 / JNK / ERK pathway. The results in vivo were consistent with those in vitro. In conclusion, overexpression of CLCA2 inhibited the progression of cervical cancer in vivo and in vitro. This may provide a theoretical basis for CLCA2 as a new indicator of clinical diagnosis and prognosis of cervical cancer or as a potential target of drug therapy.

摘要

宫颈癌是一种严重威胁全球女性身心健康的恶性肿瘤。钙激活氯离子通道蛋白（CLCA2）作为一种新型钙激活氯离子通道蛋白，在肿瘤的发生发展中发挥着重要作用。但其在宫颈癌中的作用及其确切的调控机制尚不清楚。在本研究中，我们发现 CLCA2 在宫颈癌细胞中明显下调，过表达 CLCA2 抑制宫颈癌细胞的增殖、迁移和侵袭，促进细胞凋亡，CLCA2 通过 p38/JNK/ERK 通路抑制 EMT（上皮间质转化）。体外结果与体内结果一致。综上所述，过表达 CLCA2 抑制了宫颈癌在体内和体外的进展。这可能为 CLCA2 作为宫颈癌临床诊断和预后的新指标或作为药物治疗的潜在靶点提供理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/a29f613cf113/12860_2022_440_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/cb7ad5071b71/12860_2022_440_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/19eb9014d120/12860_2022_440_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/85dcedc75392/12860_2022_440_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/1315b7f10029/12860_2022_440_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/a29f613cf113/12860_2022_440_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/cb7ad5071b71/12860_2022_440_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/19eb9014d120/12860_2022_440_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/85dcedc75392/12860_2022_440_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/1315b7f10029/12860_2022_440_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/9594891/a29f613cf113/12860_2022_440_Fig5_HTML.jpg

相似文献

[1]
CLCA2 overexpression suppresses epithelial-to-mesenchymal transition in cervical cancer cells through inactivation of ERK/JNK/p38-MAPK signaling pathways.

BMC Mol Cell Biol. 2022-10-25

[2]
Along with its favorable prognostic role, CLCA2 inhibits growth and metastasis of nasopharyngeal carcinoma cells via inhibition of FAK/ERK signaling.

J Exp Clin Cancer Res. 2018-2-20

[3]
Decreased expression of CLCA2 and the correlating with immune infiltrates in patients with cervical squamous cell carcinoma: A bioinformatics analysis.

Taiwan J Obstet Gynecol. 2021-5

[4]
Placenta growth factor promotes migration through regulating epithelial-mesenchymal transition-related protein expression in cervical cancer.

Int J Clin Exp Pathol. 2014-12-1

[5]
CLCA2 Interactor EVA1 Is Required for Mammary Epithelial Cell Differentiation.

PLoS One. 2016-3-1

[6]
CLCA2 epigenetic regulation by CTBP1, HDACs, ZEB1, EP300 and miR-196b-5p impacts prostate cancer cell adhesion and EMT in metabolic syndrome disease.

Int J Cancer. 2018-3-30

[7]
Loss of CLCA4 promotes epithelial-to-mesenchymal transition in breast cancer cells.

PLoS One. 2013-12-26

[8]
LASP2 suppresses colorectal cancer progression through JNK/p38 MAPK pathway meditated epithelial-mesenchymal transition.

Cell Commun Signal. 2017-6-12

[9]
CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion.

Cancer Biol Ther. 2012-9-18

[10]
CLCA2 suppresses the proliferation, migration and invasion of cervical cancer.

Exp Ther Med. 2021-7

引用本文的文献

[1]
Scutellaria Barbata inhibits epithelial-mesenchymal transformation through PI3K/AKT and MDM2 thus inhibiting the proliferation, migration and promoting apoptosis of Cervical Cancer cells.

PLoS One. 2025-4-16

[2]
Calcium channels as pharmacological targets for cancer therapy.

Clin Exp Med. 2025-3-25

[3]
Silencing PPAP2C inhibits lung adenocarcinoma migration and invasion via the ERK/JNK pathway.

Mol Med Rep. 2025-1

[4]
TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.

J Ovarian Res. 2024-3-25

[5]
Approach for Elucidating the Molecular Mechanism of Epithelial to Mesenchymal Transition in Fibrosis of Asthmatic Airway Remodeling Focusing on Cl Channels.

Int J Mol Sci. 2023-12-25

本文引用的文献

[1]
CLCA2 suppresses the proliferation, migration and invasion of cervical cancer.

Exp Ther Med. 2021-7

[2]
Activation of the extracellular-signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) signal pathway and osteogenic factors in subchondral bone of patients with knee osteoarthritis.

Ann Transl Med. 2021-4

[3]
Decreased expression of CLCA2 and the correlating with immune infiltrates in patients with cervical squamous cell carcinoma: A bioinformatics analysis.

Taiwan J Obstet Gynecol. 2021-5

[4]
The calcium-activated chloride channel-associated protein rCLCA2 is expressed throughout rat epidermis, facilitates apoptosis and is downmodulated by UVB.

Histochem Cell Biol. 2021-5

[5]
Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis.

Transl Oncol. 2020-11

[6]
From Orai to E-Cadherin: Subversion of Calcium Trafficking in Cancer to Drive Proliferation, Anoikis-Resistance, and Metastasis.

Biomedicines. 2020-6-21

[7]
MicroRNA-294 Promotes Cell Proliferation, Migration and Invasion in SMMC-7721 Hepatoma Carcinoma Cells by Activating the JNK/ERK Signaling Pathway.

Am J Med Sci. 2020-3-9

[8]
Survival of patients with early-stage cervical cancer after abdominal or laparoscopic radical hysterectomy: a nationwide cohort study and literature review.

Eur J Cancer. 2020-5-15

[9]
EMT Factors and Metabolic Pathways in Cancer.

Front Oncol. 2020-4-7

[10]
CLCA2 expression is associated with survival among African American women with triple negative breast cancer.

PLoS One. 2020-4-16

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