Gene interactions and pathways from curated databases and text-mining
Cancer Res 2005, PMID: 15753384

ErbB2 promotes Src synthesis and stability: novel mechanisms of Src activation that confer breast cancer metastasis.

Tan, Ming; Li, Ping; Klos, Kristine S; Lu, Jing; Lan, Keng-Hsueh; Nagata, Yoichi; Fang, Dexing; Jing, Tong; Yu, Dihua

Activation of Src kinase plays important roles in the development of many neoplasias. Most of the previous Src studies focused on the deregulation of Src kinase activity. The deregulated Src protein synthesis and stability in mediating malignant phenotypes of cancer cells, however, have been neglected. While investigating the signal transduction pathways contributing to ErbB2-mediated metastasis, we found that ErbB2-activated breast cancer cells that had higher metastatic potentials also had increased Src activity compared with ErbB2 low-expressing cells. The increased Src activity in ErbB2-activated cells paralleled higher Src protein levels, whereas Src RNA levels were not significantly altered. Our studies revealed two novel mechanisms that are involved in Src protein up-regulation and activation by ErbB2: (a) ErbB2 increased Src translation through activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway and (b) ErbB2 increased Src stability most likely through the inhibition of the calpain protease. Furthermore, inhibition of Src activity by a Src-specific inhibitor, PP2, or a Src dominant-negative mutant dramatically reduced ErbB2-mediated cancer cell invasion in vitro and metastasis in an experimental metastasis animal model. Together, activation of ErbB2 and downstream signaling pathways can lead to increased Src protein synthesis and decreased Src protein degradation resulting in Src up-regulation and activation, which play critical roles in ErbB2-mediated breast cancer invasion and metastasis.

Diseases/Pathways annotated by Medline MESH: Breast Neoplasms, Lung Neoplasms, Neoplasm Invasiveness
Document information provided by NCBI PubMed

Text Mining Data

Src → ErbB2: " ErbB2 promotes Src synthesis and stability : novel mechanisms of Src activation that confer breast cancer metastasis "

Src → ErbB2: " Our studies revealed two novel mechanisms that are involved in Src protein up-regulation and activation by ErbB2 : ( a ) ErbB2 increased Src translation through activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway and ( b ) ErbB2 increased Src stability most likely through the inhibition of the calpain protease "

rapamycin/4E-BP1 → ErbB2: " Our studies revealed two novel mechanisms that are involved in Src protein up-regulation and activation by ErbB2 : ( a ) ErbB2 increased Src translation through activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway and ( b ) ErbB2 increased Src stability most likely through the inhibition of the calpain protease "

Akt/mammalian → ErbB2: " Our studies revealed two novel mechanisms that are involved in Src protein up-regulation and activation by ErbB2 : ( a ) ErbB2 increased Src translation through activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway and ( b ) ErbB2 increased Src stability most likely through the inhibition of the calpain protease "

Akt/mammalian target of rapamycin/4E-BP1 → ErbB2: " Our studies revealed two novel mechanisms that are involved in Src protein up-regulation and activation by ErbB2 : ( a ) ErbB2 increased Src translation through activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway and ( b ) ErbB2 increased Src stability most likely through the inhibition of the calpain protease "

rapamycin/4E-BP1 pathway and ( b ) → ErbB2: " Our studies revealed two novel mechanisms that are involved in Src protein up-regulation and activation by ErbB2 : ( a ) ErbB2 increased Src translation through activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway and ( b ) ErbB2 increased Src stability most likely through the inhibition of the calpain protease "

Src → ErbB2: " Together, activation of ErbB2 and downstream signaling pathways can lead to increased Src protein synthesis and decreased Src protein degradation resulting in Src up-regulation and activation, which play critical roles in ErbB2 mediated breast cancer invasion and metastasis "

Manually curated Databases

No curated data.