Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tumour suppressor PTEN, also named MMAC1 or TEP1, is associated with a number of malignancies in human populations. This protein has a dual protein phosphatase activity, being also capable to dephosphorylate phosphatidylinositol 3,4,5 triphosphate. We have studied the mechanism of growth suppression attributable to PTEN. We observed that PTEN overexpression inhibits cell growth in a variety of normal and transformed, human and murine cells. Bromodeoxyuridine (BrdU) incorporation and TUNEL labelling experiments in transiently transfected cells demonstrate that this inhibition is due to a cell cycle arrest rather than induction of apoptosis. Given that PTEN is unable to cause cell growth arrest in retinoblastoma (Rb)-deficient cell lines, we have explored the possible requirement for pRb in the PTEN-induced inhibition of cell proliferation. We found that the co-expression of SV40 antigen, but not a mutant form (which binds exclusively to p53), and cyclin D1/cdk4 are able to overcome the PTEN-mediated growth suppression. In addition, the reintroduction of a functional pRb, but not its relatives p107 or p130, in Rb-deficient cells restores the sensitivity to PTEN-induced arrest. Finally, the hyperphosphorylation of transfected pRb is inhibited by PTEN co-expression and restored by PI-3K co-expression. Accordingly, PTEN gene is mostly expressed, in parallel to Akt, in mid-late G1 phase during cell cycle progression prior to pRb hyperphosphorylation. Finally, we have studied the signal transduction pathways modulated by PTEN expression. We found that PTEN-induced growth arrest can be rescued by the co-expression of active PI-3K and downstream effectors such as Akt or PDK1, and also certain small GTPases such as Rac1 and Cdc42, but not by active Ha-ras, raf or RhoA. Collectively, our data link the tumour suppressor activities of PTEN to the machinery controlling cell cycle through the modulation of signalling molecules whose final target is the functional inactivation of the retinoblastoma gene product.
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PMID:PTEN tumour suppressor is linked to the cell cycle control through the retinoblastoma protein. 1060 5

Cervical cancer continues to be among the most frequent gynaecologic cancers worldwide. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway is constitutively activated in cervical cancer. Inositol polyphosphate 4-phosphatase type II (INPP4B) is a phosphoinositide phosphatase and considered a negative regulatory factor of the PI3K/AKT pathway. INPP4B has diverse roles in various tumours, but its role in cervical cancer is largely unknown. In this study, we investigated the role of INPP4B in cervical cancer. Overexpression of INPP4B in HeLa, SiHa and C33a cells inhibited cell proliferation, metastasis and invasiveness in CCK-8, colony formation, anchorage-independent growth in soft agar and Transwell assay. INPP4B reduced the expression of some essential proteins in the PI3K/AKT/SGK3 pathway including p-AKT, p-SGK3, p-mTOR, phospho-p70S6K and PDK1. In addition, overexpression of INPP4B decreased xenograft tumour growth in nude mice. Loss of INPP4B protein expression was found in more than 60% of human cervical carcinoma samples. In conclusion, INPP4B impedes the proliferation and invasiveness of cervical cancer cells by inhibiting the activation of two downstream molecules of the PI3K pathway, AKT and SGK3. INPP4B acts as a tumour suppressor in cervical cancer cells.
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PMID:INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway. 2951 42

Abnormal expression of microRNAs (miRNAs) contributes to tumour growth and invasion. MiR-326 expression often down-regulates in several kinds of cancer and low expression of miR-326 is linked with poor prognosis in cancer patients. In the present study, we aimed to explore the modulatory mechanism of miR-326 in hepatocellular carcinoma (HCC). miR-326 expression was significantly decreased in HCC cell lines and tissues. miR-326 decreased HCC cell growth by affecting cell-cycle progression and by promoting apoptosis. In addition, miR-326 inhibited HCC cell invasion by decreasing the EMT phenotype. We found that miR-326 functioned as a tumour suppressor by repressing its down-stream target PDK1. C-myc contributed to miR-326 down-regulation through binding at its promoter and inhibited its expression. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying miR-326. Restoration of miR-326 reduced tumour growth in vivo. Our findings suggest that miR-326 may be a candidate prognostic biomarker and a target for new therapies in HCC patients.
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PMID:Gold nano-particles (AuNPs) carrying miR-326 targets PDK1/AKT/c-myc axis in hepatocellular carcinoma. 3129 47