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

Abstract

"Abstract 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, pan-creatic, 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, sug-gesting 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 dis-puted; 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. Keywords: growth/differentiation factor-15, GDF-15, epithelial–mesenchymal transition, EMT, colorectal cancer, metastasis, prognostic."