Suppression of LIM and SH3 Domain Protein 1 (LASP1) Negatively Regulated by Androgen Receptor Delays Castration Resistant Prostate Cancer Progression

Dejima, Takashi; Imada, Kenjiro; Takeuchi, Ario; Shiota, Masaki; Leong, Jeffrey; Tombe, Tabitha; Tam, Kevin J.; Fazli, Ladan; Naito, Seiji; Gleave, Martin; Ong, Christopher J.

doi:10.1002/pros.23269

Cited by 11 publications

(4 citation statements)

References 37 publications

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“…The result revealed that cyclin D1 was also downregulated in these cells; however, phosphorylation of ERK was upregulated by drug treatment in BT-549 and UACC-812 cells (Figure 4c). Considering that the same phenomenon of increased ERK phosphorylation has been observed in a castration-sensitive prostate cancer cell line, LNCaP cells, in a previous study (Dejima et al, 2017), this might have been a result of negative feedback caused by growth inhibition induced by AR antagonists.…”

Section: Ar Antagonists Downregulated Cyclin D1 In Breast Cancer Cellssupporting

confidence: 75%

Analysis of the responsiveness to antiandrogens in multiple breast cancer cell lines

Kuroiwa,

Ito,

Nakayama

et al. 2024

Genes to Cells

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Antiandrogens were originally developed as therapeutic agents for prostate cancer but are also expected to be effective for breast cancer. However, the role of androgen signaling in breast cancer has long been controversial due to the limited number of experimental models. Our study aimed to comprehensively investigate the efficacy of antiandrogens on breast cancer. In the present study, a total of 18 breast cancer cell lines were treated with the agonist or antagonists of the androgen receptor (AR). Among the 18 cell lines tested, only T‐47D cells proliferated in an androgen‐dependent manner, while the other cell lines were almost irresponsive to AR stimulation. On the other hand, treatment with AR antagonists at relatively high doses suppressed the proliferation of not only T‐47D cells but also some other cell lines including AR‐low/negative cells. In addition, expression of the full‐length AR and constitutively active AR splice variants, AR‐V7 and ARV567es, was not correlated with sensitivity to AR antagonists. These data suggest that the antiproliferative effect of AR antagonists is AR‐independent in some cases. Consistently, proliferation of AR‐knockout BT‐549 cells was inhibited by AR antagonists. Identification of biomarkers would be necessary to determine which breast cancer patients will benefit from these drugs.

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Section: Ar Antagonists Downregulated Cyclin D1 In Breast Cancer Cellssupporting

confidence: 75%

Analysis of the responsiveness to antiandrogens in multiple breast cancer cell lines

Kuroiwa,

Ito,

Nakayama

et al. 2024

Genes to Cells

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“…In addition, our study showed that knockdown of LASP-1 expression induced G2 phase accumulation; besides, knockdown of LASP-1 leads to decreased expression of cyclin A and cyclin B, and increased phospho-cdc2 (Tyr15) expression (37). Our study demonstrated that silencing of LASP1 significantly inhibited prostate cancer cell growth by decreasing cyclin D1 and increasing p21 and p27 (38). Migration and invasion are key determinants of cancer cell progression and metastasis.…”

Section: Discussionmentioning

confidence: 59%

Role of LASP-1, a novel SOX9 transcriptional target, in the progression of lung cancer

Shi

Guo

2017

Int J Oncol

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Lung cancer accounts for most cancer-related deaths worldwide. However, the underlying mechanism by which it mediates the progression of lung cancer remains unclear. Expression of LASP-1 (LIM and SH3 protein 1) was evaluated in lung cancer tissues and tumor-adjacent normal tissues using immunohistochemistry and western blotting. Functional studies have shown that siRNA-mediated silencing of LASP-1 in human lung cancer cells and reduced cell proliferation, migration, and invasion. Flow cytometry and immunofluorescence staining also revealed that rate of cell apoptosis was increased after knockdown of expression of LASP-1, thereby suggesting that LASP-1 may function as an oncogene during lung cancer progression. SOX9 is an important transcription factor, which is involved in the development of several types of human cancer. Further analysis has showed the presence of a consensus-binding site of SOX9 in the promoter region of LASP-1. Mechanistic investigations showed that LASP-1 was transcriptionally activated by SOX9. Through luciferase reporter and ChIP assays, we demonstrated that LASP-1 was a direct target gene of sex determining region Y-box 9 (SOX9). Knockdown of SOX9 expression by RNA interference reduces cell proliferation and induces apoptosis of lung cancer cells, which was consistent with the results obtained from silencing the expression of LASP-1 in NCI‑H1650 cells. Together, these findings indicated that LASP-1, as a downstream target of SOX9, may act as a novel biomarker for lung cancer and plays an important role in cell proliferation, migration, and invasion.

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“…Further studies have reported that LASP1 is involved in cellular migration, invasion, proliferation and apoptosis through several mechanisms, such as participation in signaling pathways, m6A methylation modification or influencing the tumor microenvironment (30)(31)(32)(33)(34). In addition, progress has been made in terms of ongoing therapeutic research seeking to target LASP1 (35). Therefore, LASP1 is widely regarded as a prognostic marker for determining tumor prognosis (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

lncRNA PAARH impacts liver cancer cell proliferation by engaging miR‑6512‑3p to target LASP1

Wei,

Liu,

Huang

et al. 2024

Oncol Lett

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Long non-coding (lnc)RNAs serve a pivotal role as regulatory factors in carcinogenesis. The present study aimed to assess the involvement of the lncRNA progression and angiogenesis-associated RNA in hepatocellular carcinoma (PAARH) in liver cancer, along with the associated underlying mechanism. Through the use of reverse transcription-quantitative (RT-q)PCR, differences in the expression levels of PAARH in HepG2, HEP3B2.1.7, HCCLM3, Huh-7 and MHCC97-H liver cancer cell lines and THLE-2 epithelial cell lines were evaluated. The liver cancer cell line with the greatest, significantly different, level of expression relative to the normal liver cell line was selected for subsequent experiments. Using ENCORI database, the putative target genes of the microRNA (miR) miR-6512-3p were predicted. Cells were then transfected with lentiviruses carrying short-hairpin-PAARH to interfere with PAARH expression. Subsequently, HepG2 liver cancer cells were transfected with a miR-6512-3p mimic and an inhibitor, and the expression levels of miR-6512-3p and the LIM and SH3 domain protein 1 (LASP1) in cells were assessed using RT-qPCR analysis. Cell proliferation was subsequently evaluated using colony formation assays, and immunofluorescence and western blotting were used to assess the expression level of LASP1 in transfected cells. The binding interaction between miR-6512-3p and LASP1 was further evaluated using a dual-luciferase reporter gene assay. Liver cancer cells were found to exhibit higher expression levels of PAARH compared with normal liver cells. Following PAARH interference, the expression level of miR-6512-3p was significantly increased, whereas that of LASP1 was significantly decreased, resulting in a reduction in cell proliferation. In liver cancer cells, miR-6512-3p overexpression led to a significant reduction in the LASP1 level and reduced proliferation, whereas suppressing miR-6512-3p led to a significant increase in LASP1 levels and increased proliferation. Additionally, the inhibition of miR-6512-3p caused the states of low LASP1 expression and reduced cell proliferation to be reversed. LASP1, a recently identified target gene of miR-6512-3p, was demonstrated to be suppressed by miR-6512-3p overexpression, thereby inhibiting liver cancer cell proliferation. Taken together, the findings of the present study demonstrate that the lncRNA PAARH may enhance liver cancer cell proliferation by engaging miR-6512-3p to target LASP1.

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Suppression of LIM and SH3 Domain Protein 1 (LASP1) Negatively Regulated by Androgen Receptor Delays Castration Resistant Prostate Cancer Progression

Cited by 11 publications

References 37 publications

Analysis of the responsiveness to antiandrogens in multiple breast cancer cell lines

Analysis of the responsiveness to antiandrogens in multiple breast cancer cell lines

Role of LASP-1, a novel SOX9 transcriptional target, in the progression of lung cancer

lncRNA PAARH impacts liver cancer cell proliferation by engaging miR‑6512‑3p to target LASP1

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