Article Data

  • Views 464
  • Dowloads 128

Original Research

Open Access

Knockdown of GDF15 inhibits endometrial cancer cell proliferation and EMT

  • Litao Yu1,*,
  • Jing Shi2
  • Kedan Cao1

1Department of Obstetrics and Gynecology, Changzhou Maternal and Child Health Care Hospital, 213000 Changzhou, Jiangsu, China

2Department of Gastroenterology, Changzhou Tumor Hospital, 213000 Changzhou, Jiangsu, China

DOI: 10.22514/ejgo.2024.053 Vol.45,Issue 3,June 2024 pp.95-101

Submitted: 12 February 2024 Accepted: 09 April 2024

Published: 15 June 2024

*Corresponding Author(s): Litao Yu E-mail: tli_yu0311@163.com

Abstract

Endometrial cancer (EC) is a malignant tumor affecting the uterine upper layer. Despite recent advancements, identifying new therapeutic targets remains important for improving patient prognosis. Growth differentiation factor 15 (GDF15) belongs to the Transforming Growth Factor (TGF)-β superfamily and is often upregulated in pathological conditions, including injury and cancers. However, its involvement in EC remains poorly understood. This study aims to elucidate the significance of GDF15 in EC and its potential underlying mechanism. Our results indicate increased GDF15 expression levels in EC tissues, and the knockdown of GDF15 was found to suppress EC cell growth and epithelial-mesenchymal transition (EMT). Moreover, GDF15 depletion inhibited the TGF-β pathway activation. In summary, GDF15 can promote EC cell growth and EMT by modulating the TGF-β/Smad2/Smad3 axis.


Keywords

Endometrial cancer (EC); Growth differentiation factor 15 (GDF15); Growth; EMT; TGF-β/Smad2/Smad3 axis


Cite and Share

Litao Yu,Jing Shi,Kedan Cao. Knockdown of GDF15 inhibits endometrial cancer cell proliferation and EMT. European Journal of Gynaecological Oncology. 2024. 45(3);95-101.

References

[1] Khatun M, Urpilainen E, Ahtikoski A, Arffman RK, Pasanen A, Puistola U, et al. Low expression of stanniocalcin 1 (STC-1) protein is associated with poor clinicopathologic features of endometrial cancer. Pathology Oncology Research. 2021; 27: 1609936.

[2] Chen Y, You S, Li J, Zhang Y, Kokaraki G, Epstein E, et al. Follicular helper T-cell-based classification of endometrial cancer promotes precise checkpoint immunotherapy and provides prognostic stratification. Frontiers in Immunology. 2021; 12: 788959.

[3] Yang X, Li X, Cheng Y, Zhou J, Shen B, Zhao L, et al. Comprehensive analysis of the glycolysis-related gene prognostic signature and immune infiltration in endometrial cancer. Frontiers in Cell and Developmental Biology. 2021; 9: 797826.

[4] Kozłowski M, Borzyszkowska D, Mirko J, Turoń-Skrzypińska A, Piotrowska K, Tołoczko-Grabarek A, et al. Preoperative serum levels of PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 in the diagnosis of endometrial cancer. Cancers. 2023; 15: 4815.

[5] Pölcher M, Rottmann M, Brugger S, Mahner S, Dannecker C, Kiechle M, et al. Lymph node dissection in endometrial cancer and clinical outcome: a population-based study in 5546 patients. Gynecologic Oncology. 2019; 154: 65–71.

[6] Wu H, Zhang J. Decreased expression of TFAP2B in endometrial cancer predicts poor prognosis: a study based on TCGA data. Gynecologic Oncology. 2018; 149: 592–597.

[7] Tubridy EA, Taunk NK, Ko EM. Treatment of node-positive endometrial cancer: chemotherapy, radiation, immunotherapy, and targeted therapy. Current Treatment Options in Oncology. 2024; 25: 330–345.

[8] Medina-Gutierrez E, Cespedes MV, Gallardo A, Rioja-Blanco E, Pavon MA, Asensio-Puig L, et al. Novel endometrial cancer models using sensitive metastasis tracing for CXCR4-targeted therapy in advanced disease. Biomedicines. 2022; 10: 1680.

[9] Ngamjariyawat A, Cen J, Wang X, Welsh N. GDF15 protects insulin-producing beta cells against pro-inflammatory cytokines and metabolic stress via increased deamination of intracellular adenosine. International Journal of Molecular Sciences. 2024; 25: 801.

[10] Lu JF, Zhu MQ, Xia B, Zhang NN, Liu XP, Liu H, et al. GDF15 is a major determinant of ketogenic diet-induced weight loss. Cell Metabolism. 2024; 36: 454–456.

[11] Joo M, Kim D, Lee MW, Lee HJ, Kim JM. GDF15 promotes cell growth, migration, and invasion in gastric cancer by inducing STAT3 activation. International Journal of Molecular Sciences. 2023; 24: 2925.

[12] Kim-Muller JY, Song L, LaCarubba Paulhus B, Pashos E, Li X, Rinaldi A, et al. GDF15 neutralization restores muscle function and physical performance in a mouse model of cancer cachexia. Cell Reports. 2023; 42: 111947.

[13] Zhao X, Liu X, Hu S, Pan Y, Zhang J, Tai G, et al. GDF15 contributes to radioresistance by mediating the EMT and stemness of breast cancer cells. International Journal of Molecular Sciences. 2022; 23: 10911.

[14] Park H, Nam KS, Lee HJ, Kim KS. Ionizing radiation-induced GDF15 promotes angiogenesis in human glioblastoma models by promoting VEGFA expression through p-MAPK1/SP1 signaling. Frontiers in Oncology. 2022; 12: 801230.

[15] Li L, Zhang R, Yang H, Zhang D, Liu J, Li J, et al. GDF15 knockdown suppresses cervical cancer cell migration in vitro through the TGF-β/Smad2/3/Snail1 pathway. FEBS Open Bio. 2020; 10: 2750–2760.

[16] Lin H, Luo Y, Gong T, Fang H, Li H, Ye G, et al. GDF15 induces chemoresistance to oxaliplatin by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis in colorectal cancer. To be published in Cellular Oncology. 2024. [Preprint].

[17] Zheng X, Ma N, Wang X, Hu J, Ma X, Wang J, et al. Exosomes derived from 5-fluorouracil-resistant colon cancer cells are enriched in GDF15 and can promote angiogenesis. Journal of Cancer. 2020; 11: 7116–7126.

[18] Kim J, Kim SH, Kang H, Lee S, Park SY, Cho Y, et al. TFEB-GDF15 axis protects against obesity and insulin resistance as a lysosomal stress response. Nature Metabolism. 2021; 3: 410–427.

[19] Tektonidou MG, Papassotiriou I, Sfikakis PP. Growth differentiation factor 15 (GDF-15) as potential cardiovascular risk biomarker in antiphospholipid syndrome. Rheumatology. 2021; 61: 394–399.

[20] Rochette L, Zeller M, Cottin Y, Vergely C. GDF15: an emerging modulator of immunity and a strategy in COVID-19 in association with iron metabolism. Trends in Endocrinology & Metabolism. 2021; 32: 875–889.

[21] Xiang X, Bhowmick K, Shetty K, Ohshiro K, Yang X, Wong LL, et al. Mechanistically based blood proteomic markers in the TGF-beta pathway stratify risk of hepatocellular cancer in patients with cirrhosis. Genes & Cancer. 2024; 15: 1–14.

[22] Fu Y, Zhou Y, Mu Y, Lv Y, Chen G, Zhang H, et al. Testicular orphan receptor 4 induced hepatic stellate cells activation via the regulation of TGF-β receptor Ⅰ/Smad2/3 signaling pathway. Annals of Hepatology. 2023; 28: 100775.

[23] Wang P, Zhang T, Jiang N, Wang K, Feng L, Liu T, et al. PDIA6, which is regulated by TRPM2-AS/miR-424-5p axis, promotes endometrial cancer progression via TGF-beta pathway. Cell Death & Disease. 2023; 14: 829.

[24] Zhao T, Sun R, Ma X, Wei L, Hou Y, Song K, et al. Overexpression of LPCAT1 enhances endometrial cancer stemness and metastasis by changing lipid components and activating the TGF/β-Smad2/3 signaling pathway. Acta Biochimica et Biophysica Sinica. 2022; 54: 904–916.

[25] Park HN, Song MJ, Choi YE, Lee DH, Chung JH, Lee ST. LRG1 Promotes ECM integrity by activating the TGF-β signaling pathway in fibroblasts. International Journal of Molecular Sciences. 2023; 24: 12445.

[26] Zhang Q, Fong CC, Yu WK, Chen Y, Wei F, Koon CM, et al. Herbal formula Astragali Radix and Rehmanniae Radix exerted wound healing effect on human skin fibroblast cell line Hs27 via the activation of transformation growth factor (TGF-β) pathway and promoting extracellular matrix (ECM) deposition. Phytomedicine. 2012; 20: 9–16.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top