MARCKS contributes to stromal cancer-associated fibroblast activation and facilitates ovarian cancer metastasis

Yang, Zongyuan; Xu, Sen; Park, Jin; Yang, Xin; Li, Xiaoting; Wan, Dongyi; Zhang, Taoran; Long, Sixiang; Wu, Xiao; Chen, Gang; Li, Meng; Liú, Dan; Fang, Yong; Chen, Pingbo; Ma, Ding; Gao, Qinglei

doi:10.18632/oncotarget.8726

Cited by 32 publications

(35 citation statements)

References 62 publications

(69 reference statements)

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“…S1F). These results were consistent with previous findings (19,21,22) and implicated that CAFs could promote peritoneal metastasis of ovarian cancer.…”

Section: Cxcl14 Is Overexpressed In Cafs Of Metastatic Lesion Of Ovarsupporting

confidence: 94%

Long Noncoding RNA LINC00092 Acts in Cancer-Associated Fibroblasts to Drive Glycolysis and Progression of Ovarian Cancer

et al. 2017

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The majority of patients with epithelial ovarian cancer are diagnosed at a late stage when the peritoneal metastases exist; however, there is little knowledge of the metastatic process in this disease setting. In this study, we report the identification of the long noncoding RNA LINC00092 as a nodal driver of metastatic progression mediated by cancer-associated fibroblasts (CAF). Prometastatic properties of CAFs and were found to associate with elevated expression of the chemokine CXCL14. In clinical specimens, elevated levels of CXCL14 in CAFs also correlated with poor prognosis. Notably, CXCL14-high CAFs mediated upregulation of LINC00092 in ovarian cancer cells, the levels of which also correlated with poor prognosis in patients. Mechanistic studies showed that LINC00092 bound a glycolytic enzyme, the fructose-2,6-biphosphatase PFKFB2, thereby promoting metastasis by altering glycolysis and sustaining the local supportive function of CAFs. Overall, our study uncovered a positive feedback loop in the metabolism of CXCL14-positive CAFs and ovarian cancer cells that is critical for metastatic progression. .

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“…S1F). These results were consistent with previous findings (19,21,22) and implicated that CAFs could promote peritoneal metastasis of ovarian cancer.…”

Section: Cxcl14 Is Overexpressed In Cafs Of Metastatic Lesion Of Ovarsupporting

confidence: 94%

Long Noncoding RNA LINC00092 Acts in Cancer-Associated Fibroblasts to Drive Glycolysis and Progression of Ovarian Cancer

et al. 2017

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“…Since the MARCKS protein was identified in the early 1980s, its role in regulating cell movement has been extensively studied. MARCKS plays important roles during embryonic development (9,10) and in tumor progression (14,34). However, the expression levels and function of MARCKSL1 in lung cancer remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, MARCKS may serve as a novel biomarker and therapeutic target for cancer, as metastasis is associated with changes in cell morphology and cell migration. Upregulation of MARCKS has been shown to promote the progression of several types of cancer, such as prostate cancer (11), osteosarcoma (12), breast cancer (13), ovarian cancer (14) and hepatocellular carcinoma (15).…”

Section: Introductionmentioning

confidence: 99%

MARCKSL1 promotes the proliferation, migration and invasion of lung adenocarcinoma cells

et al. 2020

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Lung cancer is the most common cancer in males and females and ~40% of lung cancer cases are adenocarcinomas. Previous studies have demonstrated that myristoylated alanine rich protein kinase C substrate (MARCKS) is upregulated in several types of cancer and is associated with poor prognosis in patients with breast cancer. However, its expression level and role in lung adenocarcinoma remain unknown. Therefore, the aim of the present study was to investigate the expression level and biological functions of MARCKS like 1 (MARCKSL1), a member of the MARCKS family, in lung adenocarcinoma. The expression level of MARCKSL1 was examined in human lung adenocarcinoma tissues and cell lines. MARCKSL1-specific small interfering RNAs effectively suppressed its expression level and significantly inhibited the proliferation, migration and invasion of lung adenocarcinoma cells. Additionally, the role of MARCKSLI in the regulation of metastasis was examined. Silencing MARCKSL1 decreased the expression of the epithelial-mesenchymal transition (EMT)-associated proteins E-cadherin, N-cadherin, vimentin and snail family transcriptional repressor 2, and decreased the phosphorylation level of AKT. The results obtained in the current study suggested that MARCKSL1 promoted the progression of lung adenocarcinoma by regulating EMT. MARCKSLI may have prognostic value and serve as a novel therapeutic target in lung adenocarcinoma.

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“…Ovarian cancer accounts for only 4% of malignant tumors in women, but it has the highest mortality rate among all gynecological malignant tumor types (3,4). Recurrence and early metastasis of tumor cells are the primary reasons for the poor prognosis of patients with ovarian cancer (5).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑138 inhibits SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells

Zhu

Jin

2018

Exp Ther Med

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The aim of the present study was to investigate the expression and biological functions of microRNA (miR)-138 in ovarian cancer at the tissue and cellular levels, as well as its underlying mechanisms. A total of 47 patients with ovarian cancer were included in the present study. Ovarian cancer tissues were subjected to staging classification according to the FIGO 2000 criteria. Lymphatic metastasis was also examined. Ovarian cancer A2780 cells were transfected using liposomes. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of miR-138. A Cell-Counting Kit 8 assay was used to examine cell viability, while a Transwell assay was employed to study cell invasion and migration. The effects of miR-138 on SOX12 protein expression were examined by western blot analysis. A dual luciferase reporter assay was performed to identify the direct interaction between miR-138 and SOX12 gene. Expression of miR-138 was downregulated in ovarian cancer tissues. The level of miR-138 in patients with ovarian cancer with lymphatic metastasis was significantly lower compared with patients without lymphatic metastasis. However, expression of miR-138 was not associated with the stage of ovarian cancer. Upregulation of miR-138 inhibited the proliferation and suppressed the invasion and migration of A2780 cells. SOX12 promoted the proliferation, invasion and migration of A2780 cells. In addition, miR-138 downregulated the expression of SOX12 via binding with the 3′-UTR of SOX12 gene. The present study demonstrates that miR-138 expression is downregulated in ovarian cancer tissues and miR-138 acts as a tumor suppressor gene by inhibiting SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells.

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MARCKS contributes to stromal cancer-associated fibroblast activation and facilitates ovarian cancer metastasis

Cited by 32 publications

References 62 publications

Long Noncoding RNA LINC00092 Acts in Cancer-Associated Fibroblasts to Drive Glycolysis and Progression of Ovarian Cancer

Long Noncoding RNA LINC00092 Acts in Cancer-Associated Fibroblasts to Drive Glycolysis and Progression of Ovarian Cancer

MARCKSL1 promotes the proliferation, migration and invasion of lung adenocarcinoma cells

MicroRNA‑138 inhibits SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells

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