Spondin 1 promotes metastatic progression through Fak and Src dependent pathway in human osteosarcoma

Chang, Heping; Dong, Tieli; Ma, Xiaoting; Zhang, Tao; Chen, Zhaoyu; Yang, Zongyou; Zhang, Yingze

doi:10.1016/j.bbrc.2015.05.092

Cited by 25 publications

(26 citation statements)

References 24 publications

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“…The role of FAK in cell migration is well-characterized, and tumor progression and metastasis can be promoted by FAK signaling pathways through their regulation of cell migration, invasion, epithelial to mesenchymal transition and angiogenesis [ 9 , 10 ]. There was evidence from a previous study that increased phosphorylated form of FAK and Src via activation by the extracellular matrix glycoprotein, Spondin 1, promoted cell invasiveness and pulmonary metastatic progression of osteosarcoma [ 45 ]. Thus, overexpression of pFAK-Y397 may participate in the worse progression of osteosarcoma patients with metastases.…”

Section: Discussionmentioning

confidence: 99%

pFAK-Y397 overexpression as both a prognostic and a predictive biomarker for patients with metastatic osteosarcoma

et al. 2017

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Focal adhesion kinase (FAK) is important for tumor cell survival and metastasis in various cancers. However, its expression and prognostic value in patients with metastatic osteosarcoma remain unknown. We investigated the expression of FAK and its phosphorylated form (pFAK-Y397) in osteosarcoma tissues from 53 patients by immunohistochemistry and evaluated their correlations with clinicopathologic characteristics and outcomes. The prognostic values were assessed using Kaplan-Meier survival and Cox regression analyses. Total FAK and pFAK-Y397 were overexpressed in 48 (90.6%) and 33 (62.3%) cases, respectively. pFAK-Y397 overexpression was correlated with poor histologic response after neoadjuvant chemotherapy in patients with osteosarcoma regardless of the presence of metastasis or not. Kaplan-Meier curve showed that patients with metastatic osteosarcoma with pFAK-Y397 overexpression had significantly worse overall survival (OS) than those with non-overexpression (P = 0.044). Multivariate Cox regression analysis confirmed pFAK-Y397 overexpression as an independent prognostic predictor for OS and post metastases OS (PMOS) (P = 0.017, P = 0.006, respectively). Age at diagnosis was also an independent indicator for PMOS (P = 0.003). However, total FAK expression was not correlated with any clinicopathologic characteristics or OS in patients with metastatic osteosarcoma. In conclusion, our findings identified FAK as a common aberrant protein overexpression in various subtypes of osteosarcoma. pFAK-Y397 overexpression can be used as a prognostic biomarker predicting poor OS for patients with metastatic osteosarcoma, and the expression of pFAK-Y397 differentiated good and poor responders to neoadjuvant chemotherapy.

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Section: Discussionmentioning

confidence: 99%

pFAK-Y397 overexpression as both a prognostic and a predictive biomarker for patients with metastatic osteosarcoma

et al. 2017

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“…The relevance of FAK/Src in cell migration and invasive processes extends to other cellular systems. For instance, the cell adhesion protein Spondin 1, involved in the attachment of sensory neuron cells and growth of neurites, also promotes cell migration and invasion through a FAK/Srcdependent pathway in human osteosarcoma cell lines [60]. Further, Src is also associated with cell permeability, EMT, migration, invasion and metastasis of tumor cells [61].…”

Section: Discussionmentioning

confidence: 99%

Leptin induces cell migration and invasion in a FAK-Src- dependent manner in breast cancer cells

Juárez-Cruz

Zuñiga-Eulogio

Olea-Flores

et al. 2019

Preprint

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Breast cancer is the most common invasive neoplasia, and the second leading cause of death associated with cancer in women worldwide. Mammary tumorigenesis is severely linked to obesity, the potential connection is leptin. Leptin is a hormone secreted by adipocytes, which contributes to the progression of breast cancer. Cell migration, metalloproteases secretion, and invasion are cellular processes associated with various stages of metastasis. These processes are regulated by the kinases FAK and Src. In this study, we utilized the breast cancer cell lines MCF7 and MDA-MB-231to determine the effect of leptin on FAK and Src kinases activation, cell migration, metalloproteases secretion, and invasion. By Western blot we found that leptin activates FAK and Src, and induces the localization of FAK to the focal adhesions. Specific inhibitors of FAK and Src showed that the effect exerted by leptin in cell migration, and invasion in breast cancer cells is dependent on these kinases. Moreover, by gelatin zymmography we established that leptin promotes the secretion of the extracellular matrix remodelers, MMP-2 and MMP-9, in a FAK and Src dependent manner. Our findings strongly suggest that leptin promotes the development of a more aggressive invasive phenotype in mammary cancer cells.

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“…SPARC has been shown to be expressed in metastatic prostate primary tumors (37), and evaluation of SPARC in primary prostate cancer could be used as a prognostic marker of metastatic progression (36). Spondin 1 contributes to osteosarcoma metastatic progression (38). Our data also showed upregulation of COL12A1 and COL6A3.…”

Section: Discussionmentioning

confidence: 99%

Structure and Function of a Prostate Cancer Dissemination–Permissive Extracellular Matrix

Penet

Kakkad

Pathak

et al. 2017

Clinical Cancer Research

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Purpose The poor prognosis of metastatic prostate cancer continues to present a major challenge in prostate cancer treatment. The tumor extracellular matrix (ECM) plays an important role in facilitating metastasis. Here we investigated the structure and function of an ECM that facilitates prostate cancer metastasis by comparing orthotopic tumors that frequently metastasize, to poorly metastatic subcutaneous tumors. Experimental Design Both tumors were derived from a human prostate cancer PC3 cell line engineered to fluoresce under hypoxia. Second harmonic generation (SHG) microscopy was used to characterize collagen 1 (Col1) fiber patterns in the xenografts as well as in human samples. Magnetic resonance imaging (MRI) was used to determine albumin-Gd-diethylenetriaminepentaacetate (alb-GdDTPA) transport through the ECM using a saturation recovery MR method combined with fast T1 SNAPSHOT-FLASH imaging. Cancer associated fibroblasts (CAFs) were also quantified in these tumors. Results Significant structural and functional differences were identified in the prometastatic orthotopic tumor ECM compared to the less metastatic subcutaneous tumor ECM. The significantly higher number of CAFs in orthotopic tumors may explain the higher Col1 fiber volumes in these tumors. In vivo, alb-GdDTPA pooling was significantly elevated in metastatic orthotopic tumors, consistent with the increased Col1 fibers. Conclusions Developing noninvasive MRI indices of macromolecular transport, together with characterization of Col1 fiber patterns and CAFs can assist in stratifying prostate cancers for aggressive treatments or active surveillance. These results highlight the role of CAFs in supporting or creating aggressive cancers, and the importance of depleting CAFs to prevent metastatic dissemination in prostate cancer.

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Spondin 1 promotes metastatic progression through Fak and Src dependent pathway in human osteosarcoma

Cited by 25 publications

References 24 publications

pFAK-Y397 overexpression as both a prognostic and a predictive biomarker for patients with metastatic osteosarcoma

pFAK-Y397 overexpression as both a prognostic and a predictive biomarker for patients with metastatic osteosarcoma

Leptin induces cell migration and invasion in a FAK-Src- dependent manner in breast cancer cells

Structure and Function of a Prostate Cancer Dissemination–Permissive Extracellular Matrix

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