Androgen receptor signaling fuels prostate cancer and is a major therapeutic target. However, mechanisms of resistance to therapeutic androgen ablation are not well understood. Here, using a prostate cancer mouse model, Ptenpc−/−, carrying a prostate epithelial-specific Pten deletion, we show that the αvβ6 integrin is required for tumor growth in vivo of castrated as well as of non-castrated mice. We describe a novel signaling pathway that couples the αvβ6 integrin cell surface receptor to androgen receptor via activation of JNK1 and causes increased nuclear localization and activity of androgen receptor. This downstream kinase activation by αvβ6 is specific for JNK1 with no involvement of p38 or ERK kinase. In addition, differential phosphorylation of Akt is not observed under these conditions, nor is cell morphology affected by αvβ6 expression. This pathway, which is specific for αvβ6, since is not regulated by a different αv containing integrin, αvβ3, promotes up-regulation of survivin which in turn supports anchorage-independent growth of αvβ6 expressing cells. Consistently, both αvβ6 and survivin are significantly increased in prostatic adenocarcinoma, but are not detected in normal prostatic epithelium. Neither XIAP nor Bcl-2 is affected by αvβ6 expression. In conclusion, we show that αvβ6 expression is required for prostate cancer progression including castrate resistant prostate cancer; mechanistically, by promoting activation of JNK1, the αvβ6 integrin causes androgen receptor increased activity in the absence of androgen, and consequent up-regulation of survivin. These preclinical results pave the way for further clinical development of αvβ6 antagonists for prostate cancer therapy.

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We propose a compact multi-parameter fibre sensing module based on a fibre Bragg grating (FBG) in single–multi–single mode fibre structure (FBG-in-SMS). We experimentally demonstrated that the FBG-in-SMS can measure temperature and strain simultaneously. In addition, we found that the process of writing FBG in SMS could be an effective technique for tuning and optimizing SMS spectrum for sensing.