# The Oncogenic Role of Serum Marker GDF15 in Promoting Colorectal Tumorigenesis via EMT and Stemness

## TL;DR

This study shows that GDF15 promotes colorectal cancer by increasing tumor growth, spread, and stem cell-like properties.

## Contribution

The study reveals GDF15's oncogenic role in CRC through EMT and stemness for the first time.

## Key findings

- GDF15 overexpression increases CRC cell proliferation, migration, and invasion.
- GDF15 induces EMT and enhances cancer stemness by upregulating key markers.
- High serum GDF15 levels correlate with advanced CRC stages and poor prognosis.

## Abstract

Growth Differentiation Factor 15 (GDF15), a stress‐responsive cytokine, is involved in the progression of various cancers. However, its precise functional role and underlying mechanism in colorectal cancer (CRC) remain unclear.

GDF15 expression in CRC was analyzed using public databases and validated in patient tissues by Western blot. Functional assays, including colony formation, CCK‐8, wound‐healing, and Transwell, were performed on LOVO and HCT116 cells following GDF15 overexpression or knockdown to assess proliferation, migration, and invasion. Epithelial‐mesenchymal transition (EMT) and stemness markers were examined by Western blot. Cancer stem cell properties were evaluated using a tumorsphere formation assay.

GDF15 was significantly upregulated in CRC tissues at both mRNA and protein levels. In vitro, GDF15 overexpression in LOVO cells promoted proliferation, migration, and invasion and induced EMT, as evidenced by downregulated E‐cadherin and upregulated vimentin and N‐cadherin. Conversely, GDF15 knockdown in HCT116 cells produced opposite effects. Furthermore, GDF15 enhanced CRC cell stemness, increasing tumorsphere formation and upregulating stemness markers (CD133, SALL4, OCT4, NANOG). Clinically, high serum GDF15 levels were significantly associated with advanced age, late TNM stage, and elevated CEA, indicating its correlation with aggressive disease features.

Our findings demonstrate that GDF15 acts as a tumor promoter in CRC by driving EMT, facilitating proliferation and metastasis, and enhancing cancer stemness. This study identifies GDF15 as a potential biomarker and therapeutic target for CRC.