GDF-15 Signaling Leading to Epithelial-to-Mesenchymal Transition in Colorectal Cancer – a Literature Review

Author(s) :

Cristina Lungulescu1, Daniel Sur2,3, Ștefan Răileanu4, Ștefania Maria Dumitru4, Elena Adriana Mateianu5, Cristian Virgil Lungulescu6

1 Doctoral School, University of Medicine and Pharmacy Craiova,  Romania.

2 Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania.

3 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400012 Cluj-Napoca, Romania.

4 Department of Oncology, Filantropia Clinical Hospital, Craiova, Romania

5 ”Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, Romania

6 University of Medicine and Pharmacy of Craiova, Department of Oncology, Craiova, Romania

Corresponding author: Daniel Sur, Email:

Published: Volume II, Issue I, July 2022, 1-7, , , - DOI:

Open Access

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July 1, 2022 0 Comments


Importance: The epithelial-mesenchymal transition (EMT) is a well-established process leading to metastasis, which is responsible for the majority of cancer-related deaths. EMT represents a critical step in the development of tumors, and is distinguishable through specific characteristics in tumor cells, such as the ability to invade and resist pharmacological treatments. Growth differentiation factor 15 (GDF-15) is a distinct member of the transforming growth factor β (TGF- β) superfamily which increases metastasis of cells both in vitro and in vivo by inducing EMT.

Observations: High GDF-15 levels in certain cancers, including endometrial, prostate, pancreatic, and colorectal cancer (CRC), may be associated with poor clinical outcomes. Higher plasma concentrations of GDF-15 have been linked to an increased risk of developing CRC and colorectal CRC-related mortality prior to a diagnosis of CRC. It has been observed that surgical excision of CRC reduces serum GDF-15, which increases when the tumor progresses, and that monitoring serum levels after surgery may aid in the prediction of cancer recurrence. However, data showed that GDF-15 regulation promoted 5-Fluorouracil (5-FU) resistance in colon cancer and GDF-15 overexpression can re-sensitize 5-FU-resistant tumor cells to chemotherapy, suggesting that GDF-15 may function as a tumor suppressor gene in colon cancer.

Conclusions: Functional investigations of GDF-15’s role in malignancy are scarce and disputed; prior findings indicate overexpression of GDF-15 in cancers, which contrasts GDF-15’s potential role as a tumor suppressor. A thorough understanding of the regulatory mechanisms of EMT may lead to significant advancements in the treatment and prevention of cancer

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