DLC2/StarD13 plays a role of a tumor suppressor in astrocytoma

El-Sitt, Sally; Khalil, Bassem D.; Hanna, Samer; El-Sabban, Marwan; Fakhreddine, Najla; El‐Sibai, Mirvat

doi:10.3892/or.2012.1819

Cited by 20 publications

(34 citation statements)

References 25 publications

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“…Consistently, StarD13 overexpression using a GFP vector led to an increase in cell death, as shown by the exclusion method, and a decrease in cell proliferation by the WST-1 and MTT assays. This was consistent with several previous studies carried out on astrocytoma and breast cancer cell lines in our laboratory (47). Accordingly, StarD13 appears to play a role as a tumor suppressor in different types of cancers particularly colorectal cancer cells, consistent with previous findings.…”

Section: Discussionsupporting

confidence: 94%

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Effect of StarD13 on colorectal cancer proliferation, motility and invasion

et al. 2013

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Colon cancer is a cancer of the epithelial cells lining the colon. It is mainly divided into different stages according to the invasiveness and metastatic ability of the tumor. Many mutations are acquired which leads to the development of this malignancy. These occur in entities that greatly affect the cell cycle, cell signaling pathways and cell motility, which all involve the action of Rho GTPases. The protein of interest in the present study was DLC2, also known as StarD13 or START-GAP2, a GTPase-activating protein (GAP) for Rho and Cdc42. Literature data indicate that this protein is considered a tumor-suppressor in hepatocellular carcinoma. Previous research in our laboratory confirmed StarD13 as a tumor suppressor in astrocytoma and in breast cancer. In the present study, we investigated the role of StarD13 in colon cancer. When overexpressed, StarD13 was found to lead to a decrease in cell proliferation in colon cancer cells. Consistently, knockdown of StarD13 led to an increase in cell proliferation. This showed that, similarly to its role in astrocytoma and breast cancer, StarD13 appears to be a tumor suppressor in colon cancer as well. We also examined the role of StarD13 in cell motility. StarD13 knockdown resulted in the inhibition of 2D cell motility. This was due to the inhibition of Rho; consequently Rac-dependent focal complexes were not formed nor detached for the cells to move forward. However, StarD13 knockdown led to an increase in 3D cell motility. Although StarD13 was indeed a tumor suppressor in our colon cancer cells, as evidenced by its effect on cell proliferation, it was required for cancer cell invasion. The present study further describes the role of StarD13 as a tumor suppressor as well as a Rho GAP.

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Section: Discussionsupporting

confidence: 94%

“…DLC-2 was also found to be overexpressed in cells exhibiting low rates of growth and proliferation (41). All the above suggest a prominent role of StarD13 as a tumor suppressor (47).…”

Section: Introductionmentioning

confidence: 96%

Effect of StarD13 on colorectal cancer proliferation, motility and invasion

et al. 2013

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“…The other study recently reported that the silencing of DLC1 in prostate cells significantly inhibits cell migration as determined by wound-healing and transwell assays, which is a result similar to our findings for DLC2 [34] Indeed, in our system, the knock down of StarD13 in HUVEC cells did not result in a significant change in cell motility in a wound healing assay (Figure S7). Interestingly, we have previously reported that the expression of StarD13 is higher in grade IV as compared to grade I human astrocytoma tissues [28]. In the same report, we presented data from REMBRANDT database showing that although the mRNA expression of StarD13 is higher in grade IV human astrocytoma samples as compared to lower grades, it was still lower than the expression in non-tumor tissues.…”

Section: Discussionmentioning

confidence: 67%

“…We have previously reported that StarD13 also plays this role in astrocytoma cells through overexpressing StarD13 [28]. In the current study, we performed pull-down assays to determine the level of Rho GTPase activation in StarD13 knock down cells.…”

Section: Resultsmentioning

confidence: 93%

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The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma cell motility

Khalil

Hanna

Saykali

et al. 2014

Experimental Cell Research

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Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Rho GTPases are small monomeric G proteins that play important roles in cytoskeleton rearrangement, cell motility, and tumor invasion. In the present study, we show that the knock down of StarD13, a GTPase activating protein (GAP) for RhoA and Cdc42, inhibits astrocytoma cell migration through modulating focal adhesion dynamics and cell adhesion. This effect is mediated by the resulting constitutive activation of RhoA and the subsequent indirect inhibition of Rac. Using Total Internal Reflection Fluorescence (TIRF)-based Förster Resonance Energy Transfer (FRET), we show that RhoA activity localizes with focal adhesions at the basal surface of astrocytoma cells. Moreover, the knock down of StarD13 inhibits the cycling of RhoA activation at the rear edge of cells, which makes them defective in retracting their tail. This study highlights the importance of the regulation of RhoA activity in focal adhesions of astrocytoma cells and establishes StarD13 as a GAP playing a major role in this process.

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Loss of STARD13 contributes to aggressive phenotype transformation and poor prognosis in papillary thyroid carcinoma

Zeng

Liang

et al. 2023

Endocrine

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DLC2/StarD13 plays a role of a tumor suppressor in astrocytoma

Cited by 20 publications

References 25 publications

Effect of StarD13 on colorectal cancer proliferation, motility and invasion

Effect of StarD13 on colorectal cancer proliferation, motility and invasion

The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma cell motility

Loss of STARD13 contributes to aggressive phenotype transformation and poor prognosis in papillary thyroid carcinoma

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