Four-and-a-half LIM protein 2 promotes invasive potential and epithelial-mesenchymal transition in colon cancer.
OBJECTIVE
Cancer invasion and metastasis may associate with the phenotype transition called epithelial-mesenchymal transition (EMT). We aim to evaluate the impact of four-and-a-half LIM protein 2 (FHL2) on EMT and invasion of colon cancer.


METHODS
The functional role of FHL2 in EMT was determined by overexpression or small interfering RNA-mediated depletion of FHL2. Mechanisms of FHL2 on expression or activity of E-cadherin and beta-catenin were assessed.


RESULTS
FHL2 was highly expressed in primary and metastatic colon cancer but not in normal tissues. FHL2 was critical for cancer cell adhesion to extracellular matrix, migration and invasion. FHL2 expression was stimulated by transforming growth factor (TGF)-beta1. Moreover, FHL2 acted as a potent EMT inducer by stimulating vimentin and matrix metalloproteinase-9 expressions and causing a loss of E-cadherin, whereas those alterations of EMT markers were not affected by silencing of Smad molecules (typical TGF-beta signal mediators) in FHL2 stable transfectant cells. Therefore, FHL2 induced EMT in a TGF-beta-dependent and Smad-independent manner. FHL2 downregulated E-cadherin expression and inhibited the formation of membrane-associated E-cadherin-beta-catenin complex. FHL2 also stabilized nuclear beta-catenin, resulting in enforcement of beta-catenin transactivation activity.


CONCLUSIONS
FHL2 is a potent EMT inducer and might be an important mediator for invasion and/or metastasis of colon cancer.
Zhang
Wenjing
W
Guangdong Provincial key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Jiang
Bo
B
Guo
Zheng
Z
Sardet
Claude
C
Zou
Bing
B
Lam
Colin S C
CS
Li
Jianming
J
He
Mingliang
M
Lan
Hui-Yao
HY
Pang
Roberta
R
Hung
I F N
IF
Tan
V P Y
VP
Wang
Jide
J
Wong
Benjamin C Y
BC
D000818:Animals; D015820:Cadherins / Q000032:analysis; D002448:Cell Adhesion; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology*; D045325:HCT116 Cells; D018398:Homeodomain Proteins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008648:Mesoderm / Q000473:pathology*; D051379:Mice; D009124:Muscle Proteins / Q000032:analysis / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; C105987:FHL2 protein, human; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors; D051176:beta Catenin