Maspin Suppresses Survival of Lung Cancer Cells through Modulation of Akt Pathway

Nam, Eun-Sook; Park, Chaehwa

doi:10.4143/crt.2010.42.1.42

Cited by 35 publications

(26 citation statements)

References 19 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Beltran and colleagues (31) demonstrated that restoration of maspin expression in NSCLC cells using artificial transcription factors combined with chromatin modifier compounds, reduced NSCLC metastatic behavior (31). Maspin was also shown to be involved in regulating the survival of lung cancer cells to chemotherapy drugs (32). Our studies showed that suppression of bIII-tubulin led to an increase in maspin expression, and that rescue of bIII-tubulin expression back into these cells was sufficient to bring maspin gene and protein expression back to control levels.…”

Section: Discussionmentioning

confidence: 99%

“…silencing PTEN in the bIII-tubulin shRNA cells restored AKT phosphorylation when the cells were exposed to adherent or nonadherent conditions. A recent study by Nam and colleagues (32) showed that overexpression of maspin in NSCLC cells resulted in a significant reduction in AKT phosphorylation that correlated with increased expression of PTEN (32). Therefore, it is tempting to speculate that the expression levels of bIII-tubulin, maspin, and PTEN are important determinants in modulating AKT activity in NSCLC cells.…”

Section: Tubb3/biii-tubulinmentioning

confidence: 99%

See 1 more Smart Citation

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

et al. 2015

View full text Add to dashboard Cite

bIII-tubulin (encoded by TUBB3) expression is associated with therapeutic resistance and aggressive disease in non-small cell lung cancer (NSCLC), but the basis for its pathogenic influence is not understood. Functional and differential proteomics revealed that bIII-tubulin regulates expression of proteins associated with malignant growth and metastases. In particular, the adhesionassociated tumor suppressor maspin was differentially regulated by bIII-tubulin. Functionally, bIII-tubulin suppression altered cell morphology, reduced tumor spheroid outgrowth, and increased sensitivity to anoikis. Mechanistically, the PTEN/AKT signaling axis was defined as a critical pathway regulated by bIII-tubulin in NSCLC cells. bIII-Tubulin blockage in vivo reduced tumor incidence and growth. Overall, our findings revealed how bIII-tubulin influences tumor growth in NSCLC, defining new biologic functions and mechanism of action of bIII-tubulin in tumorigenesis.Cancer Res; 75(2); 415-25. Ó2014 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Tubb3/biii-tubulinmentioning

confidence: 99%

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Nam et al, have shown that maspin transfection could significantly reduce AKT phosphorylation in NCI-H157 lung cancer cells, whereas, maspin knockdown increased AKT phosphorylation. 49 Currently, we do not know how maspin can regulate AKT activity. Since 22Rv1 cells contain intact PTEN which normally suppresses PI3K/ AKT signaling, one possibility is that maspin may inactivate PTEN and increase PI3K/AKT activity.…”

Section: Discussionmentioning

confidence: 99%

Snail promotes cell migration through PI3K/AKT-dependent Rac1 activation as well as PI3K/AKT-independent pathways during prostate cancer progression

Henderson

Smith²,

Burton

et al. 2015

Cell Adhesion & Migration

View full text Add to dashboard Cite

Snail, a zinc-finger transcription factor, induces epithelial-mesenchymal transition (EMT), which is associated with increased cell migration and metastasis in cancer cells. Rac1 is a small G-protein which upon activation results in formation of lamellipodia, the first protrusions formed by migrating cells. We have previously shown that Snail promotes cell migration through down-regulation of maspin tumor suppressor. We hypothesized that Snail's regulation of cell migration may also involve Rac1 signaling regulated by PI3K/AKT and/or MAPK pathways. We found that Snail overexpression in LNCaP and 22Rv1 prostate cancer cells increased Rac1 activity associated with increased cell migration, and the Rac1 inhibitor, NSC23766, could inhibit Snail-mediated cell migration. Conversely, Snail downregulation using shRNA in the aggressive C4-2 prostate cancer cells decreased Rac1 activity and cell migration. Moreover, Snail overexpression increased ERK and PI3K/AKT activity in 22Rv1 prostate cancer cells. Treatment of Snail-overexpressing 22Rv1 cells with LY294002, PI3K/AKT inhibitor or U0126, MEK inhibitor, decreased cell migration significantly, but only LY294002 significantly reduced Rac1 activity, suggesting that Snail promotes Rac1 activation via the PI3K/AKT pathway. Furthermore, 22Rv1 cells overexpressing Snail displayed decreased maspin levels, while inhibition of maspin expression in 22Rv1 cells with siRNA, led to increased PI3K/AKT, Rac1 activity and cell migration, without affecting ERK activity, suggesting that maspin is upstream of PI3K/AKT. Overall, we have dissected signaling pathways by which Snail may promote cell migration through MAPK signaling or alternatively through PI3K/AKT-Rac1 signaling that involves Snail inhibition of maspin tumor suppressor. This may contribute to prostate cancer progression.

show abstract

“…Western blot assay was performed as previously described [18]. Blots were incubated with horseradish peroxidase-conjugated secondary antibody for 1 h at room temperature and visualized by an enhanced chemiluminescence method (Amersham Pharmacia Biotech, UK).…”

Section: Methodsmentioning

confidence: 99%

Omega-3-Polyunsaturated Fatty Acids Suppress Pancreatic Cancer Cell Growth in vitro and in vivo via Downregulation of Wnt/Beta-Catenin Signaling

et al. 2011

View full text Add to dashboard Cite

Maspin Suppresses Survival of Lung Cancer Cells through Modulation of Akt Pathway

Cited by 35 publications

References 19 publications

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

Snail promotes cell migration through PI3K/AKT-dependent Rac1 activation as well as PI3K/AKT-independent pathways during prostate cancer progression

Omega-3-Polyunsaturated Fatty Acids Suppress Pancreatic Cancer Cell Growth in vitro and in vivo via Downregulation of Wnt/Beta-Catenin Signaling

Contact Info

Product

Resources

About