2. Academic Validation
  3. Nodal promotes colorectal cancer survival and metastasis through regulating SCD1-mediated ferroptosis resistance

Nodal promotes colorectal cancer survival and metastasis through regulating SCD1-mediated ferroptosis resistance

  • Cell Death Dis. 2023 Mar 31;14(3):229. doi: 10.1038/s41419-023-05756-6.
Tianqi Wu # 1,  Jian Wan # 2,  Xiao Qu # 1,  Kai Xia 1,  Fangtao Wang 1,  Zichao Zhang 1,  Muqing Yang 1,  Xiaocai Wu 1,  Renyuan Gao 1,  Xiaoqi Yuan 1,  Lin Fang 3,  Chunqiu Chen 4,  Lu Yin 5
Affiliations

Affiliations

  • 1 Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
  • 2 Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Nantong, 226000, China.
  • 3 Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. fanglin2017@126.com.
  • 4 Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. chenchunqiu6@126.com.
  • 5 Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. yinlumaster0105@126.com.
  • # Contributed equally.
PMID: 37002201 DOI: 10.1038/s41419-023-05756-6
Abstract

Re-expression of an embryonic morphogen, Nodal, has been seen in several types of malignant tumours. By far, studies about Nodal's role in colorectal Cancer (CRC) remain limited. Ferroptosis is essential for CRC progression, which is caused by cellular redox imbalance and characterized by lipid peroxidation. Herein, we observed that Nodal enhanced CRC cell's proliferative rate, motility, invasiveness, and epithelial-mesenchymal transition (EMT) in vivo and in vitro. Notably, Nodal overexpression induced monounsaturated fatty acids synthesis and increased the lipid unsaturation level. Nodal knockdown resulted in increased CRC cell lipid peroxidation. Stearoyl-coenzyme A desaturase 1 (SCD1) inhibition at least partially abolished the resistance of Nodal-overexpressing cells to RSL3-induced Ferroptosis. Mechanistically, SCD1 was transcriptionally up-regulated by SMAD2/3 pathway activation in response to Nodal overexpression. Significant Nodal and SCD1 up-regulation were observed in CRC tissues and were associated with CRC metastasis and poor clinical outcomes. Furthermore, bovine serum albumin nanoparticles/si-Nodal nanocomplexes targeting Nodal had anti-tumour effects on CRC progression and metastasis. This research elucidated the role of Nodal in CRC development and revealed a potential gene-based therapeutic strategy targeting Nodal for improving CRC treatment.

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