LGR5 is required for the maintenance of spheroid-derived colon cancer stem cells.
Colon cancer stem cells (CCSCs) are involved in colon cancer and promote tumor progression and recurrence. LGR5, a marker for intestinal stem cells (ISCs), is also considered to serve as a marker for CCSCs. However, the precise function of LGR5 in CCSCs is unclear. In this study, we demonstrated that LGR5 was highly expressed in CCSCs-enriched HT29 spheroid cells. Downregulation of LGR5 with small interfering RNA (siRNA) decreased the expression of stem the cell markers CD133 and CD44 in HT29 spheroid cells. In addition, silencing of LGR5 inhibited cell proliferation, secondary tumor sphere formation and induced cell apoptosis, and G0/G1 phase arrest in vitro by modulating Bcl-2, Bcl-xL and Bax. Knockdown of LGR5 enhanced chemosensitivity and reduced the invasive ability of HT29 spheroid cells. Moreover, LGR5-siRNA suppressed tumorigenicity of HT29 spheroid cells in vivo. The findings suggested that LGR5 plays a vital role in the maintenance of CCSCs and is a potential therapeutic target for colon cancer.
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Xiang
X
Chen
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Bo
B
Wei
Central Laboratory, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Xiaoyan
X
Han
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Zongheng
Z
Zheng
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Jianglong
J
Huang
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Jianpei
J
Liu
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Yong
Y
Huang
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Hongbo
H
Wei
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C116884:LGR5 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D002945:Cisplatin; D005472:Fluorouracil