A new study analyzes the transcriptome characteristics of triple-negative breast cancer (TNBC) patients, and identifies and confirms the novel inhibitor Wwox protein of JAK2/STAT3 signaling in breast cancer, elucidating abnormal attenuation of Wwox and abnormal activation of JAK2/STAT3 Such a negative correlation is an important cause of the metastasis of highly malignant TNBC. The study of Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis is published online in Nature-Communication.
In recent years, the incidence of breast cancer in China has continued to rise. TNBC is a type with a high degree of malignancy. Its invasiveness is extremely strong, the risk of distant metastasis is large, and the prognosis is extremely poor. At present, its treatment is relatively simple, mainly chemotherapy, and it is easy to relapse and metastasize. Endocrine therapy and molecular targeted therapy are ineffective against TNBC compared to other types of breast cancer.
The researchers screened transcriptomic analysis of TNBC cells and normal breast cells to obtain abnormal expression of multiple signals in the IL6/JAK2/STAT3 pathway, demonstrating the high abnormal expression of IL6 in TNBC cells and the persistence of JAK2/STAT3 activation. Activation may be an important factor in the distal metastasis of TNBC. The study also found that SOCS3, the main inhibitor of JAK2/STAT3, was not inhibited in TNBC; the newly discovered fragile site gene Wwox persisted in the IL6/JAK2/STAT3 signaling pathway in breast cancer. Specific inhibition occurs during activation. The researchers demonstrated the inhibitory effect of Wwox on sustained phosphorylation of STAT3 signaling and sustained activation in vivo. Wwox has been shown to be a common type of fragile sites (CFSs) in the human genome, and CFSs are prone to cleavage, which affects the coding of related functional genes. Researchers based on in vitro and in vivo and clinical evidence have shown that Wwox is significantly less expressed in TNBC than other types of breast cancer and is inversely associated with abnormal activation of IL6/JAK2/STAT3. This study demonstrates for the first time the strong inhibition of Wwox on the hyperphosphorylation and sustained activation of tumor cell JAK2/STAT3, and the mechanism of Wwox is expected to provide targets and clues for the individualized treatment of TNBC.
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