Fibroblast activation protein in osteosarcoma cells promotes angiogenesis via AKT and ERK signaling pathways

Zeng, Chao; Wen, Ming; Liu, Xiaomei

doi:10.3892/ol.2018.8027

Cited by 11 publications

(10 citation statements)

References 28 publications

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“…Since the discovery of FAP, early research focused mainly on its structure, distribution, and double enzymatic activity. However, recent studies have shown that FAP could be over-expressed on the surface of certain tumor cells (14,(28)(29)(30). Some studies found that the proliferation and migration capacity of tumor cells increased significantly after the lentiviral transfection of the FAP-overexpression plasmid, suggesting that FAP could serve as an oncogene and activate potential signaling pathways like PI3K and FAK (15,32,33), but results contradicting these findings have also been produced (15).…”

Section: Discussionmentioning

confidence: 99%

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The prognostic significance of fibroblast activation protein-α in human lung adenocarcinoma

Shi¹,

Hou²,

Yan³

et al. 2020

Ann Transl Med

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Background: Fibroblast activation protein (FAP) is a type II cell surface-bound integral serine protease, which is an important biomarker of cancer-associated fibroblasts. FAP-α performs several biological activities, including remolding extracellular matrix and acting as an immunosuppressor in the tumor microenvironment. However, the proliferation role of FAP-α in human lung adenocarcinoma has not been fully elucidated. Methods:The expression of FAP-α in 94-paired human lung adenocarcinoma tissues was identified by immunohistochemistry test. The effect of FAP on cell proliferation was examined by CCK-8 assay. RNAsequencing and bioinformatics analysis were utilized to investigate the underlying mechanism. Western blot analysis, quantitative polymerase chain reaction (qPCR), and nude mice experiments, were also conducted for further validation.Results: The proliferation rates of human fibroblast strains FAP-HFF and FAP-BJ, and human lung adenocarcinoma cell line FAP-SPC-A-1 were higher than those of controls. The nude mice experiment also showed that FAP could promote the proliferation of SPC-A-1 cell line in vivo. qPCR and Western blot analysis indicated that CCNB1 was upregulated by the overexpression of FAP in the lung adenocarcinoma cell line. The expression of FAP-α was higher in both the cytoplasm and stroma of lung adenocarcinoma than in adjacent normal tissues. Survival analysis indicated that patients with higher expression of FAP-α in tumor stroma had a poor prognosis (P=0.019). The Cancer Genome Atlas Program (TCGA) data also showed that the expression of FAP within tumor tissues was higher (in both cytoplasm and stroma) compared with that in normal tissues (P<0.05).Conclusions: Our study indicates that FAP-α could facilitate the proliferation of lung adenocarcinoma cells and can be a prognostic marker in human lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

“…Recent research indicates that the high expression of FAP in some tumors can often predict poor prognosis in malignancies like colorectal cancer (11), esophageal squamous cancer (12), and lung squamous cell carcinoma (13). However, FAP may also play a restraining role in other tumors (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

The prognostic significance of fibroblast activation protein-α in human lung adenocarcinoma

Shi¹,

Hou²,

Yan³

et al. 2020

Ann Transl Med

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“…The ERK and phosphoinositide 3-kinase/AKT signaling pathways serve an important role in a multitude of cellular functions, including cell proliferation (21), survival (22), migration (23), apoptosis (24,25) and angiogenesis (15). However, whether ERK or AKT can function as downstream targets of Rab23 remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…ab150077; 1:4,000; Abcam) at room temperature for 1.5 h. Signals on the membrane were detected using ECL reagents (Pierce; Thermo Fisher Scientific, Inc., Waltham, MA, USA). The results were quantified using Image-Pro software (version 5.1; Media Cybernetics, Inc., Rockville, MA, USA) (15).…”

Section: Methodsmentioning

confidence: 99%

Rab23 contributes to the progression of colorectal cancer via protein kinase B and extracellular signal‑regulated kinase signaling pathways

2019

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The role of Ras-related protein Rab23 in tumors has attracted increasing attention in recent years; however, whether it can function as an oncogenic protein remains under debate, and its role in colorectal cancer (CRC) is currently unknown. In the present study, high expression of Rab23 in CRC tissues was confirmed using immunohistochemistry, and high expression of Rab23 in CRC cells (SW1116 and HT29) was confirmed using reverse transcription-polymerase chain reaction and western blot analysis. A positive association of Rab23 with tumor size and advanced clinical stage was confirmed by χ 2 analysis. In addition, the positive association of Rab23 with poor disease-free survival was confirmed by survival analysis. Cell experiments further demonstrated that overexpression of Rab23 increased the expression of the proliferation marker Ki-67 and the proliferative ability in SW1116 and HT29 cells. Molecular mechanism research revealed that the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signaling pathways contributed to the high expression of Ki-67 and increased the proliferative ability induced by Rab23 in CRC cells. In conclusion, the study confirmed the high expression of Rab23 in CRC, and its positive association with CRC progression and poor prognosis. Furthermore, the data demonstrated that Rab23 increased the proliferation of CRC cells via the ERK and AKT signaling pathways. These results suggest that Rab23 may be used as a protein for diagnosis and prognosis prediction in patients with CRC, and is proposed to be a novel therapeutic target for improving the patient outcome.

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“…Modulation of TIMP3, MMP1, MMP3, MMP11 have been shown to influence in vitro invasiveness of OS cells, and enhance in vivo tumorigenicity (34)(35)(36). OS cell interactions with local stromal cells such as mesenchymal stem cells (37) and endothelial cells (38,39), have been found to be pro-tumorigenic, whereas interactions with natural killer cells (40) or primed dendritic cells (41), were shown to have anti-tumor effects.…”

Section: Biology Of Pulmonary Metastases Dissemination From the Primamentioning

confidence: 99%

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression

2020

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Osteosarcoma is a malignant primary tumor of bone, arising from transformed progenitor cells with osteoblastic differentiation and osteoid production. While categorized as a rare tumor, most patients diagnosed with osteosarcoma are adolescents in their second decade of life and underscores the potential for life changing consequences in this vulnerable population. In the setting of localized disease, conventional treatment for osteosarcoma affords a cure rate approaching 70%; however, survival for patients suffering from metastatic disease remain disappointing with only 20% of individuals being alive past 5 years post-diagnosis. In patients with incurable disease, pulmonary metastases remain the leading cause for osteosarcoma-associated mortality; yet identifying new strategies for combating metastatic progression remains at a scientific and clinical impasse, with no significant advancements for the past four decades. While there is resonating clinical urgency for newer and more effective treatment options for managing osteosarcoma metastases, the discovery of druggable targets and development of innovative therapies for inhibiting metastatic progression will require a deeper and more detailed understanding of osteosarcoma metastasis biology. Toward the goal of illuminating the processes involved in cancer metastasis, a convergent science approach inclusive of diverse disciplines spanning the biology and physical science domains can offer novel and synergistic perspectives, inventive, and sophisticated model systems, and disruptive experimental approaches that can accelerate the discovery and characterization of key processes operative during metastatic progression. Through the lens of trans-disciplinary research, the field of comparative oncology is uniquely positioned to advance new discoveries in metastasis biology toward impactful clinical translation through the inclusion of pet dogs diagnosed with metastatic osteosarcoma. Given the spontaneous course of osteosarcoma development in the context of real-time tumor microenvironmental cues and immune mechanisms, pet dogs are distinctively valuable in translational modeling given their faithful recapitulation of metastatic disease

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Fibroblast activation protein in osteosarcoma cells promotes angiogenesis via AKT and ERK signaling pathways

Cited by 11 publications

References 28 publications

The prognostic significance of fibroblast activation protein-α in human lung adenocarcinoma

The prognostic significance of fibroblast activation protein-α in human lung adenocarcinoma

Rab23 contributes to the progression of colorectal cancer via protein kinase B and extracellular signal‑regulated kinase signaling pathways

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression

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