In vivo evidence supporting a metastasis suppressor role for Stard13 (Dlc2) in ErbB2 (Neu) oncogene induced mouse mammary tumors

Basak, Pratima; Leslie, Heather; Dillon, Rachelle L.; Muller, William J.; Raouf, Afshin; Mowat, Michael

doi:10.1002/gcc.22519

Cited by 14 publications

(10 citation statements)

References 27 publications

(65 reference statements)

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“…The StarD13 gene as a target of miR-720 could regulate the abilities of cell growth, migration and invasion in colorectal cancer [28]. Earlier in vivo mice experiments showed that StarD13 was a metastasis suppressor gene, which is consistent with our results [29].…”

Section: Discussionsupporting

confidence: 90%

Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13

Chen

et al. 2019

Cell Mol Biol Lett

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Background This study aims to investigate the effects of inhibiting microRNA-9-5p (miR-9-5p) on the expression of StAR-related lipid transfer domain containing 13 (StarD13) and the progress of prostate cancer. Methods The mRNA expression levels of miR-9-5p and StarD13 were determined in several prostate cancer cell lines. We chose DU145 and PC-3 cells for further research. The CCK8 assay was used to measure the cell viability. The cell invasion and wound-healing assays were respectively applied to evaluate invasion and migration. The expression of E-cadherin (E-cad), N-cadherin (N-cad) and vimentin were measured via western blot. DU145 and PC-3 cells overexpressing StarD13 were generated to investigate the variation in proliferation, invasion and migration. A luciferase reporter assay was used to identify the target of miR-9-5p. Results Our results show that miR-9-5p was highly expressed and StarD13 was suppressed in prostate cancer cells. MiR-9-5p inhibition repressed the cells’ viability, invasion and migration. It also increased the expression of E-cad and decreased that of N-cad and vimentin. StarD13 overexpression gave the same results as silencing of miR-9-5p: suppression of cell proliferation, invasion and migration. The bioinformatics analysis predicted StarD13 as a target gene of miR-9-5p. Quantitative RT-PCR, western blot analysis and the dual-luciferase reporter assay were employed to confirm the prediction. Conclusion Our results show that miR-9-5p plays a powerful role in the growth, invasion, migration and epithelial–mesenchymal transition (EMT) of prostate cancer cells by regulating StarD13. A therapeutic agent inhibiting miR-9-5p could act as a tumor suppressor for prostate cancer.

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Section: Discussionsupporting

confidence: 90%

Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13

Chen

et al. 2019

Cell Mol Biol Lett

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“…23 Interesting results were also presented in a work of Basak et al ., where authors showed that in the mammary cancer model the DLC2 deletion did not change the tumor growth, however it had an impact on the metastasis formation, which suggests its metastasis suppressor rather than tumor suppressor role. 24 Our results did not confirm the DLC2 deficiency as a common feature of HCC at the protein and gene levels in our experimental group. Similar results were presented in the work of Wang et al ., where authors showed that the major member of the DLC family whose expression is reduced in HCC is DLC1, while the expression of DLC2 was not diminished and even was increased in the subset of tumors.…”

Section: Discussioncontrasting

confidence: 78%

Deleted in Liver Cancer 2 (DLC2) protein expression in hepatocellular carcinoma

et al. 2019

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Deleted in Liver Cancer (DLC) proteins belong to the family of RhoGAPs and are believed to operate as negative regulators of the Rho family of small GTPases. So far, the role of the first identified member from the DLC family, DLC1, was established as a tumor suppressor in hepatocellular carcinoma. The function of its close family relative, DLC2 is unequivocal. In the present study we attempted to determine whether the loss of DLC2 is a common feature of hepatocellular carcinoma tissue. We examined two types of hepatocellular carcinoma- typical and fibrolamellar one. Our analysis revealed that DLC2 protein is not diminished in cancer tissue when compared to non-cancerous liver specimens. What is more, we observed DLC2 to be more abundantly expressed in cancer tissue, particularly in tumors with the inflammation background. In addition, we found that DLC2 gene status was diploid in virtually all tumor samples examined. Our results indicate that DLC2 is not diminished in hepatocellular carcinoma cells. It appears that members of the DLC family, although structurally highly related, may function differently in cancer cells.

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“…Furthermore, recent findings have revealed that StarD13 and its competing endogenous RNA, ceRNAs-3’UTRs inhibit breast cancer metastasis by inhibiting epithelial to mesenchymal transition (EMT) [ 65 – 67 ]. A homozygote or heterozygote loss of StarD13 in mammary tumors linked to ErbB2 (tyrosine phosphate -receptor), increased lung metastasis in vivo as well [ 68 ], further demonstrating StarD13 invasion and metastasis suppressor functions.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tumor suppressor StarD13 in invadopodia regulation

et al. 2020

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Background Lung cancer is the second most commonly occurring cancer. The ability to metastasize and spread to distant locations renders the tumor more aggressive. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in the regulation of the actin cytoskeleton and in cancer cell migration and metastasis. In this study we investigated the role of the RhoA/Cdc42 GAP, StarD13, a previously described tumor suppressor, in malignancy, migration and invasion of the lung cancer cells A549. Methods We knocked down StarD13 expression in A549 lung cancer cells and tested the effect on cell migration and invadopodia formation using time lapse imaging and invasion assays. We also performed rescue experiments to determine the signaling pathways downstream of StarD13 and transfected the cells with FRET biosensors for RhoGTPases to identify the proteins involved in invadopodia formation. Results We observed a decrease in the level of expression of StarD13 in lung tumor tissues compared to normal lung tissues through immunohistochemistry. StarD13 also showed a lower expression in the lung adenocarcinoma cell line A549 compared to normal lung cells, WI38. In addition, the depletion of StarD13 increased cell proliferation and viability in WI38 and A549 cells, suggesting that StarD13 might potentially be a tumor suppressor in lung cancer. The depletion of StarD13, however, inhibited cell motility, conversely demonstrating a positive regulatory role in cell migration. This was potentially due to the constitutive activation of RhoA detected by pull down and FRET assays. Surprisingly, StarD13 suppressed cell invasion by inhibiting Cdc42-mediated invadopodia formation. Indeed, TKS4 staining and invadopodia assay revealed that StarD13 depletion increased Cdc42 activation as well as invadopodia formation and matrix degradation. Normal lung cells depleted of StarD13 also produced invadopodia, otherwise a unique hallmark of invasive cancer cells. Cdc42 knock down mimicked the effects of StarD13, while overexpression of a constitutively active Cdc42 mimicked the effects of its depletion. Finally, immunostaining and FRET analysis revealed the absence of StarD13 in invadopodia as compared to Cdc42, which was activated in invadopodia at the sites of matrix degradation. Conclusion In conclusion, StarD13 plays distinct roles in lung cancer cell migration and invasion through its differential regulation of Rho GTPases.

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In vivo evidence supporting a metastasis suppressor role for Stard13 (Dlc2) in ErbB2 (Neu) oncogene induced mouse mammary tumors

Cited by 14 publications

References 27 publications

Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13

Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13

Deleted in Liver Cancer 2 (DLC2) protein expression in hepatocellular carcinoma

Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tumor suppressor StarD13 in invadopodia regulation

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