Sulfotransferase SULT2B1 facilitates colon cancer metastasis by promoting SCD1‐mediated lipid metabolism

Author:

Che Gang12,Wang Wankun12,Wang Jiawei3,He Cheng4,Yin Jie5,Chen Zhendong12,He Chao12,Wang Xujing12,Yang Yan12ORCID,Liu Jian12ORCID

Affiliation:

1. Department of Surgical Oncology The First Affiliated Hospital, School of Medicine Zhejiang University Hangzhou Zhejiang China

2. Center Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou Zhejiang China

3. Department of Colorectal Surgery Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University Hangzhou Zhejiang China

4. Department of Thoracic Surgery The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou Zhejiang China

5. Department of Colorectal Medicine Zhejiang Cancer Hospital Hangzhou Zhejiang China

Abstract

AbstractMetastasis is responsible for at least 90% of colon cancer (CC)‐related deaths. Lipid metabolism is a critical factor in cancer metastasis, yet the underlying mechanism requires further investigation. Herein, through the utilisation of single‐cell sequencing and proteomics, we identified sulfotransferase SULT2B1 as a novel metastatic tumour marker of CC, which was associated with poor prognosis. CC orthotopic model and in vitro assays showed that SULT2B1 promoted lipid metabolism and metastasis. Moreover, SULT2B1 directly interacted with SCD1 to facilitate lipid metabolism and promoted metastasis of CC cells. And the combined application of SCD1 inhibitor CAY with SULT2B1‐ konockout (KO) demonstrated a more robust inhibitory effect on lipid metabolism and metastasis of CC cells in comparison to sole application of SULT2B1‐KO. Notably, we revealed that lovastatin can block the SULT2B1‐induced promotion of lipid metabolism and distant metastasis in vivo. Further evidence showed that SMC1A transcriptionally upregulated the expression of SULT2B1. Our findings unveiled the critical role of SULT2B1 in CC metastasis and provided a new perspective for the treatment of CC patients with distant metastasis.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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