BackgroundTissue inhibitor matrix metalloproteinase 1 (TIMP1) plays a vital role in carcinogenesis, yet its precise functional roles and regulation remain unclear. In this study, we aim to investigate its biological function and clinical significance in human colon cancer.MethodsWe analyzed the expression of TIMP1 in both public database (Oncomine and TCGA) and 94 cases of primary colon cancer and matched normal colon tissue specimens. The underlying mechanisms of altered TIMP1 expression on cell tumorigenesis, proliferation, and metastasis were explored in vitro and in vivo.ResultsTIMP1 was overexpressed in colon tumorous tissues and lymph node metastasis specimens than in normal tissues. The aberrant expression of TIMP1 was significantly associated with the regional lymph node metastasis (p = 0.033), distant metastasis (p = 0.039), vascular invasion (p = 0.024) and the American Joint Committee on Cancer (AJCC) stage (p = 0.026). Cox proportional hazards model showed that TIMP1 was an independent prognostic indicator of disease-free survival (HR = 2.603, 95 % CI: 1.115–6.077, p = 0.027) and overall survival (HR = 2.907, 95 % CI: 1.254–6.737, p = 0.013) for patients with colon cancer. Consistent with this, our findings highlight that suppression of TIMP1 expression decreased proliferation, and metastasis but increased apoptosis by inducing TIMP1 specific regulated FAK-PI3K/AKT and MAPK pathway.ConclusionTIMP1 might play an important role in promoting tumorigenesis and metastasis of human colon cancer and function as a potential prognostic indicator for colon cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0427-7) contains supplementary material, which is available to authorized users.

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The ability to group physical stimuli into behaviorally relevant categories is fundamental to perception and cognition. Despite a large body of work on stimulus categorization at the behavioral and cognitive levels, little is known about the underlying mechanisms at the neuronal level. Here, combining mouse auditory psychophysical behavior and in vivo two-photon imaging from the auditory cortex, we investigate how sensory-to-category transformation is implemented by cortical neurons during a stimulus categorization task. Distinct from responses during passive listening, many neurons exhibited emergent selectivity to stimuli near the category boundary during task performance, reshaping local tuning maps; other neurons became more selective to category membership of stimuli. At the population level, local cortical ensembles robustly encode category information and predict trial-by-trial decisions during task performance. Our data uncover a task-dependent dynamic reorganization of cortical response patterns serving as a neural mechanism for sensory-to-category transformation during perceptual decision-making.