We demonstrate a mechanism by which EGF promotes prostate cancer cell progression through a ROS/STAT3/HIF-1α/TWIST1/N-cadherin signaling cascade, providing novel biomarkers and promising therapeutic targets for prostate cancer cell progression.

Rab coupling protein (RCP)-induced tumor cell migration has been implicated in tumor pathophysiology and patient outcomes. In the present study, we demonstrate that RCP stabilizes β1 integrin leading to increased β1 integrin levels and activation of a signaling cascade culminating in Slug induction, epithelial-to-mesenchymal transition and increased invasion. Ectopic expression of RCP induced Slug expression. Silencing β1 integrin efficiently inhibited RCP-induced Slug expression and subsequent cancer cell invasion. Conversely, ectopic expression of β1 integrin was sufficient to induce Slug expression. Pharmacological inhibition of integrin linked kinase (ILK), EGFR and NF-κB, as well as transfection of a dominant-negative mutant of Ras (RasN17), significantly inhibited RCP-induced Slug expression and cancer cell invasion. Strikingly, ectopic expression of RCP was sufficient to enhance metastasis of ovarian cancer cells to the lung. Collectively, we demonstrate a mechanism by which RCP promotes cancer cell aggressiveness through sequential β1 integrin stabilization, activation of an ILK/EGFR/Ras/NF-κB signaling cascade and subsequent Slug expression.

Lenalidomide is a potential immunomodulator that enhances the anti‐tumor effect of natural killer (NK) cells. However, the underlying molecular mechanism of anti‐tumor effects and long‐term activating effect on NK cells are unclear. Here, we report that lenalidomide in the long stimulation with interleukin‐2 (IL‐2) enhances the proliferation and specific anti‐tumor function of NK cells by modulating transcriptomic patterns, including downregulation of KLRB1 (CD161). In conclusion, the results suggest that lenalidomide may be more applicable in the field of cancer immunotherapy by exhibiting specific cytotoxicity ability enhancement of NK cells against cancer cells as well as long‐term activating effect on NK cells. Support or Funding Information The research fund was supported by Ministry of Science, Technology and Information, Republic of Korea (Grant no. 2019R1F1A1054920)

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