The involvement of JAK-STAT3 in cell motility, invasion, and metastasis

Abstract

JAK-STAT3 signaling, while regulating many aspects of cancer development and progression, promotes invasion and metastasis through activation of key metastasis promoting genes such as WASF3. STAT3 promotes WASF3 expression and JAK2 independently activates it, which is required for invasion. JAK-STAT3 signaling is dependent on WASF3 function, since its inactivation in cells expressing JAK-STAT3 suppresses invasion. WASF3 overexpression leads to activation of NFκB and ZEB1 which also promote invasion through regulation of target genes involved in metastasis. NFκB frequently cooperates with STAT3 to upregulate metastasis promoting genes such as matrix metalloproteinases and cytokines, as well as to suppress microRNAs which can suppresses invasion. This better understanding of the complex role played by JAK-STAT3 in the regulation of cell movement, invasion, and metastasis provides opportunities to suppress this lethal aspect of cancer progression by not only targeting the JAK and STAT3 proteins directly, but also some of the downstream effectors of JAK-STAT3 signaling.

Musashi-2 promotes migration and invasion in bladder cancer via activation of the JAK2/STAT3 pathway

“…Wang et al 26 uncovered that Msi2 promotes HCC cell invasion and progression via the Wnt/β-catenin signaling pathway. Jak2/STAT3 signaling has been shown to have a pivotal role in the epithelial-mesenchymal transition (EMT) to cancer cells, 16 and the importance of Jak2/STAT3 signaling in bladder cancer progression has been implicated. Zhao et al 27 showed that activation of Jak2/STAT3 in bladder cancer cells drove EMT and tumor invasion.…”

“…Previous studies have demonstrated that the JAK2/STAT3 signaling pathway has a central role in tumor metastasis, 16 which prompted us to investigate whether Msi2 is involved in regulation of the JAK2/STAT3 signaling pathway in bladder cancer. As shown in Figures 5a-c, overexpression of Msi2 significantly increased and silencing of Msi2 reduced the phosphorylation of JAK2 and its downstream effecter STAT3 in both cell lines.…”

The antipsychotic drug pimozide inhibits cell growth in prostate cancer through suppression of STAT3 activation

“…Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human malignancies, including head and neck, breast, lung, gastric, hepatocellular, colorectal and prostate cancers (27)(28)(29). Aberrantly STAT3 activation contributes to oncogenesis by preventing apoptosis, inducing cell proliferation, angiogenesis, invasion, and metastasis as well as suppressing antitumor immune responses (30,31).…”

Protrusion-localized STAT3 mRNA promotes metastasis of highly metastatic hepatocellular carcinoma cells in vitro

“…However, TP53 and EEF2 did not show any difference in expression between the two fractions ( Figure 2C). Stat3 is a member of the STAT protein family, which is involved in cell invasion and metastasis in cancer [23] . To investigate the distribution of STAT3 mRNA Knockdown of Stat3 decreases the metastatic and invasive capacity of HCCLM3 cells Signal transducer and activator of transcription 3 (STAT3) activation has been linked to the EMT program in hepatocellular carcinoma [24] , and we found that STAT3 mRNA is localized to the protrusions of HCCLM3 cells.…”