Inhibition of Cell Migration, Spreading, and Focal Adhesions by Tumor Suppressor PTEN

Tamura, Masahito; Gu, Jianguo; Matsumoto, Kazue; Aota, Shin-ichi; Parsons, Ramon; Yamada, Katsushi

doi:10.1126/science.280.5369.1614

Cited by 1,097 publications

(946 citation statements)

References 10 publications

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“…The strong positive e ect of IRS-1 on cell adhesion, incidentally, is compatible with the observation that PTEN inhibits spreading and focal adhesion (Tamura et al, 1998), by interacting with FAK (Tamura et al, 1999). PTEN actually inhibits invasion Tamura et al, 1998). Since IRS-1 activates the PI3-kinase pathway, our results are also compatible with the ®nding by Feshchenko et al (1999) that C-cbl (which is activated by PI3-kinase), facilitates spreading and adhesion of cells.…”

Section: Effect Of Irs-1 On the Growth Of Lncap Cells In Nude Micesupporting

confidence: 90%

“…Indeed, when cell-to-cell aggregation was tested on polyHEMA plates, the results were dramatic, with IRS-1 expression causing the formation of huge masses of aggregated cells. The strong positive e ect of IRS-1 on cell adhesion, incidentally, is compatible with the observation that PTEN inhibits spreading and focal adhesion (Tamura et al, 1998), by interacting with FAK (Tamura et al, 1999). PTEN actually inhibits invasion Tamura et al, 1998).…”

Section: Effect Of Irs-1 On the Growth Of Lncap Cells In Nude Micesupporting

confidence: 79%

“…As expected (Tamura et al, 1998(Tamura et al, , 1999, the introduction of a wild type PTEN in LNCaP cells markedly reduced cell adhesion to laminin, ®bronectin and collagen I and also, to a lesser extent, to collagen IV. However, the e ect of PTEN was much less evident in LNCaP/IRS-1 cells.…”

Section: Effect Of Restoration Of Pten In Lncap Cellssupporting

confidence: 72%

“…It suggests that IRS-1, in LNCaP cells, sends a signal that is not in agreement with IGF-I signaling. Our ®nding is also at variance with the results of Tamura et al (1998) on PTEN that inhibits cell motility. We do not have an explanation for these discrepancies at this moment, except the obvious possibility that IGF-I may increase cell motility by other means than IRS-1 activation.…”

Section: Effect Of Irs-1 On the Growth Of Lncap Cells In Nude Micecontrasting

confidence: 42%

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IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

et al. 2000

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LNCaP prostatic cancer cells are characterized by having a PTEN mutation, low levels of type 1 insulinlike growth factor receptor (IGF-IR) and no IRS-1, one of the major substrates of the IGF-IR. The absence of IRS-1, an activator of PI3-kinase, is compensated in these cells by the mutation in PTEN, an inhibitor of PI3-kinase. However, IGF-IR signaling in the absence of IRS-1 can cause cell di erentiation and growth arrest. We hypothesized that these three characteristics may not be unrelated, speci®cally that, together, they may favor the metastatic spread of prostatic cancer cells without decreasing their growth potential. In support of this hypothesis, we report here that: (1) IRS-1 expression increases cell adhesion and decreases cell motility; (2) over-expression of the IGF-IR, in the absence of IRS-1, causes growth arrest and (3) a combination of IGF-IR and IRS-1 restores the transformed phenotype of LNCaP cells. These ®ndings suggest a mechanism by which prostatic cancer cells can achieve metastatic potential without interfering with their growth potential.

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Section: Effect Of Irs-1 On the Growth Of Lncap Cells In Nude Micesupporting

confidence: 90%

Section: Effect Of Irs-1 On the Growth Of Lncap Cells In Nude Micesupporting

confidence: 79%

Section: Effect Of Restoration Of Pten In Lncap Cellssupporting

confidence: 72%

Section: Effect Of Irs-1 On the Growth Of Lncap Cells In Nude Micecontrasting

confidence: 42%

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IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

et al. 2000

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“…Phosphoinositol lipids have a central and well documented role in cell migration, and PTEN as a regulator of these intermediate signaling molecules has a central role in this process [17]. However the proposed role of PTEN as a protein phosphatase to FAK also has profound implications and relevance to cell migration and adhesion [18]. Taken together, the possibility that Paxillin and PTEN are part of the same molecular complex seems reasonable.…”

Section: Discussionmentioning

confidence: 99%

A novel model to identify interaction partners of the PTEN tumor suppressor gene in human bladder cancer

Herlevsen

Oxford

Ptak

et al. 2007

Biochemical and Biophysical Research Communications

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Phosphatase and tensin homolog (PTEN), deleted on chromosome 10, is a potent tumor suppressor. PTEN expression is reduced in advanced bladder cancer and reduction correlates with disease stage. To gain insights into the function of PTEN in human bladder cancer by identifying its binding partners, we developed a novel IPTG inducible PTEN expression system and evaluated this system in the PTEN null UMUC-3 human bladder cancer xenograft model. In this model, induction of PTEN in vivo resulted in reduced tumor growth. We used mass spectrometry to identify PTEN interaction partners in these cells, which identified known interaction partners Major Vault Protein (MVP) and Paxillin as well as a novel interaction partner, TRK Fused Gene (TFG). In conclusion, using a biologically relevant model system to dissect PTEN tumor suppressor function in human bladder cancer, we identified three molecules important for many cellular functions in complex with PTEN.

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Investigation of germline PTEN, p53, p16INK4A/p14ARF, and CDK4 alterations in familial glioma

et al. 2000

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Epidemiological studies suggest that some familial aggregations of glioma may be due to inherited predisposition. Many genes involved in familial cancers are frequently altered in the corresponding sporadic forms. We have investigated several genes known to be altered in sporadic gliomas for their potential contribution to familial glioma. Fifteen glioma patients with a family history of brain tumors were identified through the Mayo Clinic Department of Neurology (nine diffuse astrocytomas, two oligodendrogliomas, two mixed oligoastrocytomas, one pilocytic astrocytoma, and one pineal glioma). Eleven of the propositi had one or more first degree relative with a glioma. Lymphocyte DNA was derived from each of the patients and analyzed by polymerase chain reaction (PCR) and direct sequencing of the PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 genes. In addition, fluorescence in situ hybridization (FISH) was performed on EBV-transformed lymphocytes from each affected individual to detect germline copy number of the p16(INK4A)/p14(ARF) tumor suppressor region. A p53 germline point mutation was identified in one family with some findings of Li-Fraumeni syndrome, and a hemizygous germline deletion of the p16(INK4A)/p14(ARF) tumor suppressor region was demonstrated by FISH in a family with history of both astrocytoma and melanoma. Thus, whereas germ-line mutations of PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 are not common events in familial glioma, outside of familial cancer syndromes, point mutations of p53 and hemizygous deletions and other rearrangements of the p16(INK4A)/p14(ARF) tumor suppressor region may account for a subset of familial glioma cases. Collectively, these data lend genetic support to the heritable nature of some cases of glioma.

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Inhibition of Cell Migration, Spreading, and Focal Adhesions by Tumor Suppressor PTEN

Cited by 1,097 publications

References 10 publications

IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

A novel model to identify interaction partners of the PTEN tumor suppressor gene in human bladder cancer

Investigation of germline PTEN, p53, p16INK4A/p14ARF, and CDK4 alterations in familial glioma

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