2. Academic Validation
  3. Silencing of Epidermal Growth Factor-like Domain 8 Promotes Proliferation and Cancer Aggressiveness in Human Ovarian Cancer Cells by Activating ERK/MAPK Signaling Cascades

Silencing of Epidermal Growth Factor-like Domain 8 Promotes Proliferation and Cancer Aggressiveness in Human Ovarian Cancer Cells by Activating ERK/MAPK Signaling Cascades

  • Int J Mol Sci. 2024 Dec 31;26(1):274. doi: 10.3390/ijms26010274.
Yong-Jung Song 1 2,  Ji-Eun Kim 3,  Lata Rajbongshi 3,  Ye-Seon Lim 3,  Ye-Jin Ok 3,  Seon-Yeong Hwang 3,  Hye-Yun Park 3,  Jin-Eui Lee 3,  Sae-Ock Oh 3,  Byoung-Soo Kim 4,  Dongjun Lee 5,  Hwi-Gon Kim 1 2,  Sik Yoon 2 3
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Pusan National University Yangsan Hospital and Pusan National University College of Medicine, Yangsan 50612, Republic of Korea.
  • 2 Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea.
  • 3 Department of Anatomy and Convergence Medical Sciences, Pusan National University College of Medicine, Yangsan 50612, Republic of Korea.
  • 4 School of Biomedical Convergence Engineering, Pusan National University, Yangsan 50612, Republic of Korea.
  • 5 Department of Convergence Medicine, Pusan National University College of Medicine, Yangsan 50612, Republic of Korea.
PMID: 39796130 DOI: 10.3390/ijms26010274
Abstract

Ovarian Cancer (OC) is the second most common female reproductive Cancer and the most lethal gynecological malignancy worldwide. Most human OCs are characterized by high rates of drug resistance and metastasis, leading to poor prognosis. Improving the outcomes of patients with relapsed and treatment-resistant OC remains a challenge. This study aimed to investigate the role of epidermal growth factor-like domain 8 (EGFL8) in human OC by examining the effects of siRNA-mediated EGFL8 knockdown on Cancer progression. EGFL8 knockdown in human OC cells promoted aggressive traits associated with Cancer progression, including enhanced proliferation, colony formation, migration, invasion, chemoresistance, and reduced Apoptosis. Additionally, knockdown upregulated the expression of epithelial-mesenchymal transition (EMT) markers (Snail, Twist1, Zeb1, Zeb2, and vimentin) and Cancer stem cell biomarkers (Oct4, Sox2, Nanog, KLF4, and ALDH1A1), and increased the expression of matrix metallopeptidases (MMP-2 and MMP-9), drug resistance genes (MDR1 and MRP1), and Notch1. Low EGFL8 expression also correlated with poor prognosis in human OC. Overall, this study provides crucial evidence that EGFL8 inhibits the proliferation and Cancer aggressiveness of human OC cells by suppressing ERK/MAPK signaling. Therefore, EGFL8 may serve as a valuable prognostic biomarker and a potential target for developing novel human OC therapies.

Keywords

EMT; ERK/MAPK; cancer aggressiveness; chemoresistance; epidermal growth factor-like domain 8 (EGFL8); ovarian cancer.

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