Enhanced migration potential is a common characteristic of cancer cells induced by mechanisms that are incompletely defined. The present study was designed to investigate relationship of a new discovered cytoskeleton regulator MICAL‐L2 and the endogenous epidermal growth factor receptor (EGFR) signalling pathways in gastric cancer cell migration. Increased expression of MICAL‐L2 in gastric cancer cells up‐regulated EGFR protein level, accompanied by the increase of cell migration, whereas silencing MICAL‐L2 down‐regulated EGFR and inhibited cell migration. Expression of MICAL‐L2 was also shown positively correlated with the activation of HSP27/cytoskeleton and HSP27/β‐catenin signalling pathways that provide key mechanisms controlling cell migration. The up‐regulating effect of MICAL‐L2 on EGFR is mediated through a transcription‐independent mechanism that involves inhibiting EGFR protein degradation in lysosome. Further analysis indicated that Cdc42 activation contributed in maintaining the effect of MICAL‐L2 on EGFR stability. Furthermore analysis of clinic specimens revealed increased expression of MICAL‐L2 in carcinoma tissues and a positive correlation between MICAL‐L2 and EGFR expression levels. The above results indicate that MICAL‐L2 potentiates gastric cell migration via inhibiting EGFR degradation in lysosome via a Cdc42‐dependent manner that leads to the activation of EGFR/HSP27 signalling pathways.

High expression of ULK1 concomitant with high expression of LRPPRC may serve as useful markers for shorter BCP-free survival and OS in patients with metastatic PCa after ADT.

Aims and hypothesis: Epidermal growth factor (EGF) has been shown to induce the migration of various cancer cells. However, the underlying signaling mechanisms for EGFinduced migration of oral squamous cell carcinoma (OSCC) remain to be elucidated. WNT7A, a member of the family of 19 Wnt secreted glycoproteins, is commonly associated with tumor development. It is mostly unknown whether and, if so, how EGF modulates WNT7A in OSCC cells. The role of WNT7A in OSCC was thus investigated to explore the underlying signaling mechanisms for EGF-induced migration of OSCC.Methods: Cell migration was measured by Wound healing assay and Transwell assay. Western blotting was carried out to detect the expression of WNT7A, MMP9, b-catenin, p-AKT, and p-ERK. The cells were transfected with plasmids or siRNA to upregulate or downregulate the expression of WNT7A. The location of b-catenin was displayed by immunofluorescence microscopy. Immunohistochemistry was carried out to confirm the relation between WNT7A expression and OSCC progression.Results: The present study showed that the levels of WNT7A mRNA and protein were increased by EGF stimulation in OSCC cells. Besides, it was proved that p-AKT, but not p-ERK, mediated the expression of WNT7A protein induced by EGF. Furthermore, the inhibition of AKT activation prevented the EGF-induced increase of WNT7A and matrix metallopeptidase 9 (MMP9) expression and translocation of b-catenin from the cytoplasm to the nucleus. Moreover, histological analysis of OSCC specimens revealed an association between WNT7A expression and poor clinical prognosis of the disease. Conclusions:The data in this paper indicated that WNT7A could be a potential oncogene in OSCC and identified a novel PI3K/AKT/WNT7A/b-catenin/MMP9 signaling for EGF-induced migration of OSCC cells.

MicroRNAs play critical roles in the development and progression of human cancers. Although it has been reported that miR-106a* is downregulated in follicular lymphoma, its role in renal cell carcinoma (RCC) remains unknown. This study investigated the expression and role of miR-106a* in human RCC. Our results showed that the miR-106a* expression decreased dramatically in clinical RCC tissues and cell lines. In vitro, overexpression of miR-106a* suppressed RCC cell proliferation and S/G2 transition, whereas inhibition of miR-106a* promoted cell proliferation and S/G2 transition. It was also found that miR-106a* expression was inversely correlated with the expression of insulin receptor substrate 2 (IRS-2). IRS-2 was determined to be a direct target of miR-106a* by a luciferase reporter assay. Importantly, silencing IRS-2 resulted in the same biologic effects as those of miR-106a* overexpression in RCC cells, including inhibition of RCC cell proliferation and triggering of S/G2 cell cycle arrest with inhibition of the PI3K/Akt signaling pathway. These results indicate that miR-106a* affects RCC progression by targeting IRS-2 with suppression of the PI3K/Akt signaling pathway in RCC cells. The findings suggest miR-106a* as a novel strategy for RCC treatment.