Expression of tissue inhibitors of metalloproteinase 1 (TIMP-1) in gastric cancer tissue.

Degradation of extracellular matrix (ECM) is an essential step of invasion and metastasis of gastric cancer. The proteolysis of basement membranes depends on the balance between activities of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The aim of the study was to assess the expression of TIMP-1 in gastric cancer (GC) and interstitial inflammatory infiltrate cells within GC tissue in relation to clinico-pathological features of tumor and to estimate the prognostic significance of TIMP-1 expression for patients' survival. The presence of TIMP-1 in 54 cases of gastric cancer samples was investigated by immunohistochemistry. The expression of TIMP-1 in cancer and interstitial inflammatory infiltrate cells was evaluated in semi-quantitative scale. The immunoreactivity of TIMP-1 in cancer and inflammatory cells was positive in 100% of cases and varied from weak to intense reaction. The intensity of TIMP-1 expression increased with more advanced tumor stages and in patients who died of cancer during 2-year observation. TIMP-1 expression in interstitial inflammatory infiltrate cells was the independent prognostic factor for patients' survival. The results suggest the role of TIMP-1 in gastric tumorigenesis, although this issue requires further investigtions

Expression of tissue inhibitors of metalloproteinase 1 (TIMP-1) in gastric cancer tissue.

Degradation of extracellular matrix (ECM) is an essential step of invasion and metastasis of gastric cancer. The proteolysis of basement membranes depends on the balance between activities of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The aim of the study was to assess the expression of TIMP-1 in gastric cancer (GC) and interstitial inflammatory infiltrate cells within GC tissue in relation to clinico-pathological features of tumor and to estimate the prognostic significance of TIMP-1 expression for patients' survival. The presence of TIMP-1 in 54 cases of gastric cancer samples was investigated by immunohistochemistry. The expression of TIMP-1 in cancer and interstitial inflammatory infiltrate cells was evaluated in semi-quantitative scale. The immunoreactivity of TIMP-1 in cancer and inflammatory cells was positive in 100% of cases and varied from weak to intense reaction. The intensity of TIMP-1 expression increased with more advanced tumor stages and in patients who died of cancer during 2-year observation. TIMP-1 expression in interstitial inflammatory infiltrate cells was the independent prognostic factor for patients' survival. The results suggest the role of TIMP-1 in gastric tumorigenesis, although this issue requires further investigtions

G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling

Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface of lysosomes. They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Like the TSC complex, G3BP1 deficiency elicits phenotypes related to mTORC1 hyperactivity. In the context of tumors, low G3BP1 levels enhance mTORC1-driven breast cancer cell motility and correlate with adverse outcomes in patients. Furthermore, G3bp1 inhibition in zebrafish disturbs neuronal development and function, leading to white matter heterotopia and neuronal hyperactivity. Thus, G3BPs are not only core components of SGs but also a key element of lysosomal TSC-mTORC1 signaling