Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis

Li, Rui1,2; Liu, Xuefei1,2,3,4; Huang, Xudong1,2; Zhang, Di5; Chen, Ziming1,2; Zhang, Jialiang1,2; Bai, Ruihong1,2; Zhang, Shaoping1,2; Zhao, Hongzhe1,2; Xu, Zilan1,2; Zeng, Lingxing1,2; Zhuang, Lisha1,2; Wen, Shujuan1,2; Wu, Shaojia1,2; Li, Mei6; Zuo, Zhixiang1,2; Lin, Junzhong7; Lin, Dongxin1,2,8,9,11; Zheng, Jian1,2,9,10

2023-12-01

10.1136/gutjnl-2023-330243

GUT   影响因子和分区

0017-5749

1468-3288

ObjectiveMetastasis is the major cause of cancer death. However, what types of heterogenous cancer cells in primary tumour and how they metastasise to the target organs remain largely undiscovered.DesignWe performed single-cell RNA sequencing and spatial transcriptomic analysis in primary colorectal cancer (CRC) and metastases in the liver (lCRC) or ovary (oCRC). We also conducted immunofluorescence staining and functional experiments to examine the mechanism.ResultsIntegrative analyses of epithelial cells reveal a stem-like cell cluster with high protein tyrosine phosphatase receptor type O (PTPRO) and achaete scute-like 2 (ASCL2) expression as the metastatic culprit. This cell cluster comprising distinct subpopulations shows distinct liver or ovary metastatic preference. Population 1 (P1) cells with high delta-like ligand 4 (DLL4) and MAF bZIP transcription factor A (MAFA) expression are enriched in primary CRC and oCRC, thus may be associated with ovarian metastasis. P3 cells having a similar expression pattern as cholangiocytes are found mainly in primary CRC and lCRC, presuming to be likely the culprits that specifically metastasise to the liver. Stem-like cells interacted with cancer-associated fibroblasts and endothelial cells via the DLL4-NOTCH signalling pathway to metastasise from primary CRC to the ovary. In the oCRC microenvironment, myofibroblasts provide cancer cells with glutamine and perform a metabolic reprogramming, which may be essential for cancer cells to localise and develop in the ovary.ConclusionWe uncover a mechanism for organ-specific CRC metastasis.

colorectal cancer liver cancer stem cells ovary metastasis

SCI

英语

NI论文

其他

Gastroenterology & Hepatology

Gastroenterology & Hepatology

WOS:001112426300001

BMJ PUBLISHING GROUP

CLINICAL MEDICINE

Web of Science

1.Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Guangzhou, Peoples R China
2.Sun Yat Sen Univ, Guangdong Prov Clin Res Ctr Canc, Canc Ctr, Guangzhou, Peoples R China
3.Southern Univ Sci & Technol, Sch Med, Dept Biochem, Shenzhen, Peoples R China
4.Shenzhen Childrens Hosp, Shenzhen Inst Pediat, Shenzhen, Peoples R China
5.Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Prov Key Lab Colorectal & Pelv Floor Dis, Colorectal Surg,Dept Gen Surg,Guangdong Inst Gastr, Guangzhou, Peoples R China
6.Sun Yat Sen Univ, Dept Pathol, Canc Ctr, Guangzhou, Peoples R China
7.Sun Yat Sen Univ, Canc Ctr, Dept Colorectal Surg, Guangzhou, Peoples R China
8.Chinese Acad Med Sci & Peking Union Med Coll, Dept Etiol & Carcinogenesis, Natl Canc Ctr, Natl Clin Res Ctr,Canc Hosp, Beijing, Peoples R China
9.Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Nanjing, Peoples R China
10.Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou, Peoples R China
11.Sun Yat Sen Univ, Dept Colorectal Surg, Canc Ctr, Guangzhou, Peoples R China

Li, Rui,Liu, Xuefei,Huang, Xudong,et al. Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis[J]. GUT,2023.

Li, Rui.,Liu, Xuefei.,Huang, Xudong.,Zhang, Di.,Chen, Ziming.,...&Zheng, Jian.(2023).Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis.GUT.

Li, Rui,et al."Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis".GUT (2023).