Gene interactions and pathways from curated databases and text-mining
Cancer Lett 2012, PMID: 22033246

Smad7 acts as a negative regulator of the epidermal growth factor (EGF) signaling pathway in breast cancer cells.

Kim, Sangmin; Han, Jeonghun; Lee, Se Kyung; Koo, Minyoung; Cho, Dong Hui; Bae, Soo Youn; Choi, Min-Young; Kim, Jee Soo; Kim, Jung-Han; Choe, Jun-Ho; Yang, Jung-Hyun; Nam, Seok Jin; Lee, Jeong Eon

Although it has been suggested that smad7 blocks downstream signaling of TGF-β, the role of smad7 in the EGF signaling pathway has not been fully elucidated. We determined the effect of smad7 on EGF-induced MMP-9 expression in SKBR3 breast cancer cells. The expression of smad7 and MMP-9 was increased by EGF or TGF-β1, respectively, and further increased by EGF and TGF-β1 co-treatment. EGF induced the phosphorylation of EGFR, smad3, ERK, and JNK, and MMP-9 expression was decreased by the EGFR inhibitor, AG1478. In addition, EGF-induced MMP-9 expression was inhibited by UO126 (a MEK1/2 inhibitor) or SIS3 (a smad3 inhibitor), but not by SP600125 (a JNK inhibitor). Interestingly, EGF-induced smad3 phosphorylation was completely blocked by smad7 over-expression, but not the phosphorylation of ERK and JNK. EGF- or TGF-β1-induced MMP-9 expression was completely decreased by adenoviral-smad7 (Ad-smad7) over-expression. We also investigated the role of smad3 on EGF-induced MMP-9 expression and showed that EGF-induced MMP-9 expression was decreased by smad3 siRNA transfection, whereas EGF-induced MMP-9 expression was further increased by smad3 over-expression, as expected. This study showed that EGF-induced smad3 phosphorylation mediates the induction of MMP-9, whereas smad7 inhibits TGF-β1 as well as the EGF signaling pathway in SKBR3 cells.

Diseases/Pathways annotated by Medline MESH: Breast Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

MMP-9 → EGF: " We determined the effect of smad7 on EGF induced MMP-9 expression in SKBR3 breast cancer cells "

MMP-9 — smad7: " We determined the effect of smad7 on EGF induced MMP-9 expression in SKBR3 breast cancer cells "

smad7 → EGF: " The expression of smad7 and MMP-9 was increased by EGF or TGF-ß1, respectively, and further increased by EGF and TGF-ß1 co-treatment "

MMP-9 → EGF: " The expression of smad7 and MMP-9 was increased by EGF or TGF-ß1, respectively, and further increased by EGF and TGF-ß1 co-treatment "

EGF → EGFR: " EGF induced the phosphorylation of EGFR , smad3, ERK, and JNK, and MMP-9 expression was decreased by the EGFR inhibitor, AG1478 "

EGF → ERK: " EGF induced the phosphorylation of EGFR, smad3, ERK , and JNK, and MMP-9 expression was decreased by the EGFR inhibitor, AG1478 "

EGF → smad3: " EGF induced the phosphorylation of EGFR, smad3 , ERK, and JNK, and MMP-9 expression was decreased by the EGFR inhibitor, AG1478 "

smad3 ⊣ SIS3: " In addition, EGF induced MMP-9 expression was inhibited by UO126 ( a MEK1/2 inhibitor ) or SIS3 ( a smad3 inhibitor ), but not by SP600125 ( a JNK inhibitor ) "

MMP-9 ⊣ SIS3: " In addition, EGF induced MMP-9 expression was inhibited by UO126 ( a MEK1/2 inhibitor ) or SIS3 ( a smad3 inhibitor ), but not by SP600125 ( a JNK inhibitor ) "

MMP-9 → EGF: " In addition, EGF induced MMP-9 expression was inhibited by UO126 ( a MEK1/2 inhibitor ) or SIS3 ( a smad3 inhibitor ), but not by SP600125 ( a JNK inhibitor ) "

smad3 ⊣ ERK: " Interestingly, EGF induced smad3 phosphorylation was completely blocked by smad7 over-expression, but not the phosphorylation of ERK and JNK "

smad3 → EGF: " Interestingly, EGF induced smad3 phosphorylation was completely blocked by smad7 over-expression, but not the phosphorylation of ERK and JNK "

MMP-9 → EGF: " We also investigated the role of smad3 on EGF induced MMP-9 expression and showed that EGF induced MMP-9 expression was decreased by smad3 siRNA transfection, whereas EGF induced MMP-9 expression was further increased by smad3 over-expression, as expected "

MMP-9 — smad3: " We also investigated the role of smad3 on EGF induced MMP-9 expression and showed that EGF induced MMP-9 expression was decreased by smad3 siRNA transfection, whereas EGF induced MMP-9 expression was further increased by smad3 over-expression, as expected "

smad3 → EGF: " This study showed that EGF induced smad3 phosphorylation mediates the induction of MMP-9, whereas smad7 inhibits TGF-ß1 as well as the EGF signaling pathway in SKBR3 cells "

MMP-9 → smad3: " This study showed that EGF induced smad3 phosphorylation mediates the induction of MMP-9 , whereas smad7 inhibits TGF-ß1 as well as the EGF signaling pathway in SKBR3 cells "

Manually curated Databases

No curated data.