Recent studies revealed that emodin extracted from Chinese herbs exhibits an anticancer effect on different cancer types, including colon cancer. However, the mechanism is not well understood. In our study, we confirmed that emodin treatment inhibited cell viability and induced apoptosis in colon cancer cells. Further experiments found that emodin was also able to induce autophagy, which is indispensible for apoptosis induced by emodin. More interestingly, emodin treatment also results in mitochondrial dysfunction and ROS accumulation in colon cancer cells. Finally, we stressed that ROS accumulation is essential for autophagy and apoptosis induced by emodin. In conclusion, emodin induces apoptosis in colon cancer cells through induction of autophagy, during which ROS generation is of the essence. Our findings improve understanding of emodin's effect on colon cancer suppression and provide a new theoretical basis for colon cancer therapy.
The adaptor protein Mig-6 is a negative regulator of EGF signaling. It is shown that Mig-6 inhibits cell migration via direct interaction with the ErbB receptors, thereby inhibiting cross-phosphorylation or targeting the receptors for degradation. Mig-6 has also been shown to bind to and inhibit the Rho GTPase Cdc42 to suppress cytoskeletal rearrangement. However, the molecular mechanism(s) by which Mig-6 inhibits cell migration via Cdc42 is still not entirely clear. Here, we show that Mig-6 binding to Cdc42 is necessary and sufficient to inhibit EGF-induced filopodia formation and migration. This binding, mediated by four specific residues (I11, R12, M26, R30) in the Mig-6 CRIB domain, is essential for Mig-6 function. In addition, ectopic expression of Cdc42 reverses Mig-6 inhibition of cell migration. Mig-6 CRIB domain, alone, is sufficient to inhibit cell migration. Conversely, Mig-6 binding to EGFR is dispensable for Mig-6-mediated inhibition of cell migration. Moreover, we found that decreased Mig-6 expression correlates with cancer progression in breast and prostate cancers. Together, our results demonstrate that Mig-6 inhibition of Cdc42 signaling is critical in Mig-6 function to suppress cell migration and that dysregulation of this pathway may play a critical role in cancer development.
Tumorigenesis is closely related to the loss of control of many genes. Urokinase-type plasminogen activator receptor (uPAR), a glycolipid-anchored protein on the cell surface, is controlled by many factors in tumorigenesis and is expressed in many tumor tissues. In this review, we summarize the regulatory effects of the uPAR signaling pathway on processes and factors related to tumor progression, such as tumor cell proliferation, adhesion, metastasis, glycolysis, tumor microenvironment and angiogenesis. Overall, the evidence accumulated to date suggests that uPAR induction by tumor progression may be one of the most important factors affecting therapeutic efficacy. An improved understanding of the interactions between uPAR and its coreceptors in cancer will provide critical biomolecular information that may help to better predict the disease course and response to therapy.
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