HMGA2 regulates CD44 expression to promote gastric cancer cell motility and sphere formation.
High mobility group AT-hook 2 (HMGA2) is a transcriptional modulator that mediates motility and self-renewal in cancer stem cells. Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. GC contains a population of stem-like cells that promote tumor invasion and resistance to therapy. In the current study, we investigated the expression of HMGA2 and the cancer stem cell marker CD44 in 200 GC samples and found that HMGA2 and CD44 were significantly associated with distant metastasis, histological differentiation and poor prognosis in GC patients. Positive clinical correlations of HMGA2 with CD44 were also observed in tissue sections. In vitro, overexpression of HMGA2 promoted GC sphere formation and migration in MKN74/MKN28 cells, whereas downregulation of HMGA2 decreased GC sphere formation and migration in MKN45/MGC803 cells. In addition, western blot and immunofluorescent analyses showed that HMGA2 increased the expression of the stem cell markers CD44, ALDH1, Sox2, and Oct4 and the EMT-related factors Snail and β-catenin. In a xenograft mouse model, overexpression of HMGA2 promoted tumor growth. Further immunohistochemical (IHC) analysis showed that HMGA2 increased the expression of CD44 and β-catenin, resulting in the promotion of tumor growth. Taken together, our findings indicate that HMGA2 promotes GC cancer stem cell induction and cell motility by regulating the expression of CD44. Therefore, targeting HMGA2 in GC may be therapeutically beneficial.
Department of Pathology, Tianjin Medical University Tianjin 300070, China.
Junying
J
Sun
Department of Pathology, Tianjin Medical UniversityTianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical UniversityTianjin 300052, China; Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical UniversityTianjin 300060, China.
Baocun
B
Sun
Department of Prosthodontics, Affiliated Stomatological Hospital, Tianjin Medical University Tianjin 300070, China.
Dongwang
D
Zhu
Department of Pathology, Tianjin Medical UniversityTianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical UniversityTianjin 300052, China.
Xiulan
X
Zhao
Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University Tianjin 300060, China.
Yanhui
Y
Zhang
Department of Pathology, Tianjin Medical University Tianjin 300070, China.
Xueyi
X
Dong
Department of Pathology, Tianjin Medical UniversityTianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical UniversityTianjin 300052, China.
Na
N
Che
Department of Pathology, Tianjin Medical UniversityTianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical UniversityTianjin 300052, China.
Jing
J
Li
Department of Pathology, Tianjin Medical University Tianjin 300070, China.
Fang
F
Liu
Department of Pathology, Tianjin Medical UniversityTianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical UniversityTianjin 300052, China.
Nan
N
Zhao
Department of Pathology, Tianjin Medical UniversityTianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical UniversityTianjin 300052, China.
Danfang
D
Zhang
Department of Pathology, Tianjin Medical UniversityTianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical UniversityTianjin 300052, China.
Tieju
T
Liu
Department of Pathology, Tianjin Medical UniversityTianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical UniversityTianjin 300052, China.
Xian
X
Lin
CD44 protein; Cell migration; HMGA2 protein; cancer stem cell; gastric cancer