Detail for ERBB2


Full Name

Receptor tyrosine-protein kinase erbB-2(HER2)

Uniprot ID

Gene Name

ERBB2

NCBI ID

Related Disease

  • Breast Cancer [ref.1, 2, 3]
  • Ovarian Cancer [ref.4]

Therapy Method

Function

Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.
In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.

Reference

  • [1] Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab.
    Magnifico, A., et al. (2009). Clin Cancer Res 15(6): 2010-2021.. [ 19276287 ]
  • [2] Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors.
    Chakrabarty, A., et al. (2013). Cancer Res 73(3): 1190-1200.. [ 23204226 ]
  • [3] Targeting of preexisting and induced breast cancer stem cells with trastuzumab and trastuzumab emtansine (T-DM1).
    Diessner, J., et al. (2014). Cell Death Dis 5: e1149.. [ 24675467 ]
  • [4] Reduction of the putative CD44+CD24- breast cancer stem cell population by targeting the polyamine metabolic pathway with PG11047.
    Cirenajwis, H., et al. (2010). Anticancer Drugs 21(10): 897-906.. [ 20838207 ]

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