Adenovirus-mediated gene transfer of FKHRL1 triple mutant efficiently induces apoptosis in melanoma cells

Gómez-Gutiérrez, Jorge G.; Souza, V. C. de; Hao, Hong; Oca‐Luna, Roberto Montes de; Dong, Yan; Zhou, Huiyun; McMasters, Kelly M.

doi:10.4161/cbt.5.7.2911

Cited by 48 publications

(56 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inactivation of FOXO3a may provide an advantage in proliferation of cancer cells and accelerates tumor growth. The adenovirus-mediated transfer of constitutively active FOXO3a has been reported to induce apoptosis in melanoma cells (34), indicating that direct activation of FOXO3a might be a clinical strategy. FOXO3a may also serve as an indirect therapeutic target (35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

Forkhead Transcription Factor FOXO3a Protein Activates Nuclear Factor κB through B-cell lymphoma/leukemia 10 (BCL10) Protein and Promotes Tumor Cell Survival in Serum Deprivation

Zhang

Chen

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Forkhead Transcription Factor FOXO3a Protein Activates Nuclear Factor κB through B-cell lymphoma/leukemia 10 (BCL10) Protein and Promotes Tumor Cell Survival in Serum Deprivation

Zhang

Chen

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…FOXO3 or FKHRL1 controls numerous apoptotic and cell cycle regulators (29) and has a crucial role in the development and progression of cancer (30). Recently, a role for FOXO3 in melanoma cell survival has been proposed (31), and an apoptotic response was observed in melanoma cell lines transduced with a FOXO3 triple mutant (32). Among other targets, FOXO3 regulates the expression of Bim, a Bcl-2 family member (33) whose down-regulation by RNAi inhibits anoikis (34).…”

Section: Discussionmentioning

confidence: 99%

Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor

Segura

Hanniford

Menéndez

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

493

445

View full text Add to dashboard Cite

The highly aggressive character of melanoma makes it an excellent model for probing the mechanisms underlying metastasis, which remains one of the most difficult challenges in treating cancer. We find that miR-182, member of a miRNA cluster in a chromosomal locus (7q31-34) frequently amplified in melanoma, is commonly upregulated in human melanoma cell lines and tissue samples; this up-regulation correlates with gene copy number in a subset of melanoma cell lines. Moreover, miR-182 ectopic expression stimulates migration of melanoma cells in vitro and their metastatic potential in vivo, whereas miR-182 down-regulation impedes invasion and triggers apoptosis. We further show that miR-182 over-expression promotes migration and survival by directly repressing microphthalmiaassociated transcription factor-M and FOXO3, whereas enhanced expression of either microphthalmia-associated transcription factor-M or FOXO3 blocks miR-182's proinvasive effects. In human tissues, expression of miR-182 increases with progression from primary to metastatic melanoma and inversely correlates with FOXO3 and microphthalmia-associated transcription factor levels. Our data provide a mechanism for invasion and survival in melanoma that could prove applicable to metastasis of other cancers and suggest that miRNA silencing may be a worthwhile therapeutic strategy.microRNA ͉ cancer ͉ invasion M etastasis is a central problem in cancer, yet the mechanisms underlying a cell's ability to extravasate from the primary tumor, circulate, and invade new tissue remain poorly understood. We reasoned that melanoma, one of the most notoriously invasive neoplasia, would provide an excellent model for investigating the alterations that contribute to metastasis. Melanomas are characterized by certain well-defined genetic alterations (reviewed in ref. 1) as well as frequent chromosomal aberrations associated with tumor progression (2). Recent work has also shown that melanomas display genomic alterations involving numerous microRNA genes (3). MicroRNAs (miRNAs) are endogenous noncoding small RNAs that interfere with the translation of coding messenger RNAs (mRNAs) in a sequence-specific manner (4), often to regulate processes involved in development or tissue homeostasis (5-7). Intriguingly, dysregulation of miRNAs has been found to contribute to neoplasia (8). We decided to investigate the possible contributions of miRNA dysregulation to melanoma extravasation, migration, and invasion.We compared the expression of miRNAs in a large cohort of melanoma cell lines with that of normal melanocytes. We found that miR-182, flanked by the c-MET and BRAF oncogenes in the 7q31-34 region that is frequently amplified in melanoma (9, 10), is highly expressed in metastatic melanoma cell lines and tumors, often in association with increased copy number. Moreover, we demonstrate that antisense-mediated repression of miR-182 inhibited invasion and induced melanoma cell death, whereas ectopic miR-182 up-regulation enhanced the oncogenic activity of melanoma cells in vitro ...

show abstract

“…9 We have also previously shown that an adenovirus expressing the transcription factor FKHRL1/TM (Ad-FKHRL1/TM) efficiently induces apoptosis in SK-MEL-2 and SK-MEL-28 melanoma cells in vitro. 10 apoptosis levels in DM6 cells with CH-11 (8 and 10% apoptosis, respectively, Fig. 1C).…”

Section: Adenovirus-mediated Expression Of Mutated Forkhead Human Tramentioning

confidence: 95%

“…We have previously shown that Ad-FKHRL1/TM efficiently induces apoptosis in SK-MEL-2 and SK-MEL-28 melanoma cells independent of p53. 10 Therefore, we investigated whether Ad-FKHRL1/TM can also induce apoptosis in two other melanoma cell lines which are used to establish tumors in vivo, A2058 and DM6. 16,17 Melanoma cell killing and FKHRL1/TM expression increased in a dose-dependent fashion in both cell lines ( Fig.…”

Section: Adenovirus-mediated Expression Of Mutated Forkhead Human Tramentioning

confidence: 99%

Adenovirus-mediated expression of mutated forkhead human transcription like-1 suppresses tumor growth in a mouse melanoma xenograft model

Gómez-Gutiérrez

Egger

Hao

et al. 2012

Cancer Biology & Therapy

Self Cite

View full text Add to dashboard Cite

Adenovirus-mediated gene transfer of FKHRL1 triple mutant efficiently induces apoptosis in melanoma cells

Cited by 48 publications

References 48 publications

Forkhead Transcription Factor FOXO3a Protein Activates Nuclear Factor κB through B-cell lymphoma/leukemia 10 (BCL10) Protein and Promotes Tumor Cell Survival in Serum Deprivation

Forkhead Transcription Factor FOXO3a Protein Activates Nuclear Factor κB through B-cell lymphoma/leukemia 10 (BCL10) Protein and Promotes Tumor Cell Survival in Serum Deprivation

Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor

Adenovirus-mediated expression of mutated forkhead human transcription like-1 suppresses tumor growth in a mouse melanoma xenograft model

Contact Info

Product

Resources

About