Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells.
Fibronectin (FN), an extracellular matrix ligand, plays a pivotal role in cell adhesion, migration, and oncogenic transformation. Aberrant FN expression is associated with poor prognoses in various types of cancer, including breast cancer. In the current study, we investigated the relationship between FN induction and HER2 expression in breast cancer cells. Our results showed that the level of FN expression increased in response to HER family ligands, EGF and TGF-α in a time- and dose-dependent manner. On the other hand, EGF-induced FN expression decreased in response to trastuzumab, which is a HER2-targeted monoclonal antibody. However, EGF-induced FN expression was not affected by trastuzumab in JIMT-1 breast cancer cells, which are trastuzumab insensitive cells. Next, we introduced the HER2 gene into MDA-MB231 cells to verify the relationship between FN and HER2. The level of FN expression significantly increased in HER2-overexpressed MDA-MB231 cells. In contrast, the induction of FN by HER2 was significantly decreased in response to trastuzumab treatment. In addition, the induction of FN by HER2 was down-regulated by the MEK 1/2 specific inhibitor, U0126. Using conditioned culture media of vec- and HER2-overexpressed MDA-MB231 cells, we observed the cell morphology, adhesion, and invasion of MDA-MB231 cells. Interestingly, in conditioned culture media of HER2-overexpressed MDA-MB231 cells, the cell morphology was altered, and adhesion and invasion of MDA-MB231 cells significantly increased. In addition, our results showed that recombinant human FN augmented cell adhesion and invasion of MDA-MB231 cells while these inductions decreased in response to an FN inhibitor. Therefore, we demonstrated that the induction of FN by HER2 triggers cell adhesion and invasion capacities.
Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
Myeongjin
M
Jeon
Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
Jeongmin
J
Lee
Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
S J
SJ
Nam
Department of Life Science, Hanyang University, Seoul 133-791, Republic of Korea.
Incheol
I
Shin
Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Electronic address: paojlus@hanmail.net.
J E
JE
Lee
Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Electronic address: sangmin3005.kim@samsung.com.
Sangmin
S
Kim
D001943:Breast Neoplasms; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D048430:Cell Shape; D004815:Epidermal Growth Factor / Q000502:physiology; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D015533:Transcriptional Activation; D016211:Transforming Growth Factor alpha / Q000502:physiology
D004815:Epidermal Growth Factor; D005353:Fibronectins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; C508053:ERBB2 protein, human
Adhesion; Fibronectin; HER2; Invasion; Trastuzumab