Hes1 is involved in the self-renewal and tumourigenicity of stem-like cancer cells in colon cancer.
A small subpopulation of cancer cells with stem cell-like features might be responsible for tumour generation, progression, and chemoresistance. Hes1 influences the maintenance of certain stem cells and progenitor cells and the digestive systems. We found upregulated Hes1 in poorly differentiated cancer samples compared with well-differentiated tumour samples, and most of the adenocarcinomas exhibited significantly higher levels of Hes1 mRNA compared with that observed in matched normal colon samples. Moreover, Hes1 expression was found to be correlated with the expression of stem cell markers in colon cancer samples, and Hes1 upregulates the expression of stemness-related genes in colon cancer cells. In addition, Hes1 enhances the self-renewal properties of the stem-like cells by increasing the sizes of CD133+ cells and SP cells and the ability of tumour sphere formation. Additionally, the Hes1-overexpressing cells formed significantly larger and higher number of colonies, as determined through the colony and the soft agar assays. More importantly, Hes1 enhances the tumourigenicity of colon cancer cell lines in nude mice and exhibits a strong tumour-formation ability at a cell density of 1 × 10(3). Taken together, our data indicate that Hes1 induces stem-like cell self-renewal and increases the number of tumour-initiating cells in colon cancer.
1] Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China [2].
Fei
F
Gao
1] Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China [2].
YuQin
Y
Zhang
1] Cancer Research Institute, Southern Medical University, Guangzhou 510515, China [2].
ShengChun
S
Wang
1] Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China [2].
YuanQiang
Y
Liu
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Lin
L
Zheng
Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
JianQuan
J
Yang
Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Wei
W
Huang
Department of Radiation Oncology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, China.
YanFen
Y
Ye
Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
WeiRen
W
Luo
Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Dong
D
Xiao
D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000378:metabolism; D045325:HCT116 Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D018874:Spheroids, Cellular; D000072056:Transcription Factor HES-1; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000071916:AC133 Antigen; D015703:Antigens, CD; D051792:Basic Helix-Loop-Helix Proteins; D006023:Glycoproteins; D018398:Homeodomain Proteins; D010455:Peptides; D012333:RNA, Messenger; D000072056:Transcription Factor HES-1; C000606023:PROM1 protein, human; C000606024:Prom1 protein, mouse; C078493:HES1 protein, human