Cell Death Differ: HPV mediated EGFR signal transducting pathridges promote the proliferation of cervical cancer cells

Persistent infection with human papillomavirus (HPV) is the main cause of most cervical cancers and several other types of anal genital and oral cancer.
these cancers are mainly caused by HPV16 and HPV18.
, however, 13 other high-risk HPV types were also associated with the development of cancer.
HPV-induced malignancies are mainly driven by viral cancer-causing genes E6 and E7, which increase cell proliferation and enhance cell survival by regulating the host cell signaling path path, which eventually results in malignant transformation of infected cells.
, understanding the virus-host interactions in HPV-related diseases can help identify new therapeutic targets.
MAPK (degenerative active protein kinase) is able to convert extracellular stimuli into a series of cellular reactions, while ERK (MAPKs extracellular signal-regulating kinases) and p38 have now been shown to play a critical role in the HPV life cycle and HPV-induced transformation.
, little is known about the function of JNK (c-Jun N-end kinase).
the activation of E6-mediated JNK and the related schematics of the downstream signal transduct path, the study showed that the JNK signal pathline was activated in cervical disease and cervical cancer.
HPV E6 cancer gene induces phosphateization of JNK1/2 by combining base sequence dependence with E6 PDZ.
researchers found that using small molecular inhibitors or knocking down the JNK substrate c-Jun to block the JNK1/2 signal transducting path, can reduce cell proliferation and induce the apoptosis of cervical cancer cells.
further studies have shown that the esophysic is at least partially driven by the activation of the JNK-dependent EGFR signal, which is achieved by increasing the expression levels of the EGFR and EGFR complexes EGF and HB-EGF.
JNK/c-Jun signal promotes the invasion of cervical cancer cells, which requires the expression of the cortical-interstate conversion (EMT)-related transcription factor Slug and the interstumin marker wave protein (Vimentin).
addition, the JNK/c-Jun signal is necessary for the compositional expression of HPV E6/E7, which is essential for the growth and survival of cervical cancer cells.
The results show that there is a positive feedback loop between the EGFR signal transducting path and the expression of HPV E6/E7, and the study also determines the regulatory mechanism of HPV-mediated EGFR signal transduction and promotes the proliferation, survival and EMT process of cervical cancer cells.
, the study may provide new potential therapeutic targets for cervical cancer treatment.
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