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Hepatocyte growth factor receptor (HGF receptor) [5] [6] is a protein that in humans is encoded by the MET gene.The protein possesses tyrosine kinase activity. [7] The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor.
The structure of tivantinib in complex with the c-Met kinase domain shows that the inhibitor binds a conformation that is distinct from published kinase structures. Tivantinib strongly inhibits c-Met autoactivation by selectively targeting the inactive form of the kinase between the N- and C- lobes and occupies the ATP binding site. [21]
Elevated expression levels of c-Src were found in human breast cancer tissues compared to normal tissues. [29] [30] [31] Overexpression of Human Epidermal Growth Factor Receptor 2 (HER2), also known as erbB2, is correlated with a worse prognosis for breast cancer. [32] [33] Thus, c-Src plays a key role in the tumor progression of breast cancers.
In relation to breast tumors, somatic activating mutations in Akt and the p110α subunit of the PI3K have been detected in 3–5% and 20–25% of primary breast tumors, respectively. [27] Many breast tumors also have lower levels of PTEN, which is a lipid phosphatase that dephosphorylates phosphatidylinositol (3,4,5)-trisphosphate, thereby ...
The breast cancer bone metastasis has activated TGF-β signaling, which contributes to the formation of these lesions. [31] However, on the other hand, p53 , a well-known tumor suppressor, represses EMT by activating the expression of various microRNAs – miR-200 and miR-34 that inhibit the production of protein ZEB and SNAIL, and thus ...
19713 Ensembl ENSG00000165731 ENSMUSG00000030110 UniProt P07949 P35546 RefSeq (mRNA) NM_000323 NM_020629 NM_020630 NM_020975 NM_001355216 NM_001080780 NM_009050 RefSeq (protein) NP_065681 NP_066124 NP_001342145 NP_066124.1 NP_001074249 NP_033076 Location (UCSC) Chr 10: 43.08 – 43.13 Mb Chr 6: 118.13 – 118.17 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse The RET proto-oncogene ...
[2] [3] The resulting 65 kDa cytoplasmic Tpr-Met oncoprotein forms a dimer mediated through the Tpr leucine zipper. [4] The Tpr-Met fusion protein lacks the extracellular, transmembrane and juxtamembrane domains of c-Met receptor, and has gained the Tpr dimerization motif, which allows constitutive and ligand-independent activation of the kinase.
While relatively little is known about the role MET plays in cancer when compared to the extensive studies of EMT in tumor metastasis, MET is believed to participate in the establishment and stabilization of distant metastases by allowing cancerous cells to regain epithelial properties and integrate into distant organs. Between these two states ...