STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer

Peña, Cristina; Céspedes, María Virtudes; Lindh, Maja Bradic; Kiflemariam, Sara; Mezheyeuski, Artur; Edqvist, Per‐Henrik; Hägglöf, Christina; Birgisson, Helgi; Bojmar, Linda; Jirström, Karin; Sandström, Per; Olsson, Elin; Veerla, Srinivas; Gallardo, Alberto; Sjöblom, Tobias; Chang, Andy; Reddel, Roger R.; Mangues, Ramón; Augsten, Martin; Östman, Arne

doi:10.1158/0008-5472.can-12-1875

Cited by 146 publications

(108 citation statements)

References 38 publications

(46 reference statements)

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…Because a variety of microenvironmental factors are involved in the progression of human cancer, synergistic or additive effects of Girdin phosphorylation with those factors may be important for clinical outcome of the patients. In addition, the gene-expression profiles of CAF in individual cancers need to be considered (19)(20)(21)(22)(23). Therefore, future studies should concentrate on determining the importance of Akt-Girdin signaling in the tumor microenvironment for the evaluation of clinical outcomes of the patients with various stages of malignant tumors on an individualized basis.…”

Section: Discussionmentioning

confidence: 99%

“…CAF physically assist in the invasion of surrounding tissue by actively remodeling the ECM, subsequently providing routes that can be exploited by tumor cells (14,18). On the basis of these findings, CAF gene-expression assays have been developed as useful prognostic indicators in recent clinical studies (19)(20)(21)(22)(23). Clearly, it is important to dissect the mechanisms mediating the localization, proliferation, and activity of CAF, as such insights may lead to the development of novel therapies that target the tumor microenvironment (24).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Akt–Girdin Signaling in Cancer-Associated Fibroblasts Contributes to Tumor Progression

et al. 2015

View full text Add to dashboard Cite

PI3K-Akt signaling is critical for the development, progression, and metastasis of malignant tumors, but its role in the tumor microenvironment has been relatively little studied. Here, we report that the Akt substrate Girdin, an actin-binding protein that regulates cell migration, is expressed and activated by Akt phosphorylation in cancer-associated fibroblasts (CAF) and blood vessels within the tumor microenvironment. Lewis lung tumors grafted into mice defective in Akt-mediated Girdin phosphorylation (SA transgenic mice) exhibited a decrease in both CAF infiltration and tumor growth, compared with wild-type (WT) host control animals. Contrasting with the findings of other studies, we found that Akt-dependent phosphorylation of Girdin was not a rate-limiting step in the growth of endothelial cells. In addition, Lewis lung tumors displayed limited outgrowth when cotransplanted with CAF derived from tumor-bearing SA transgenic mice, compared with CAF derived from tumor-bearing WT mice. Collectively, our results revealed a role for Akt-mediated Girdin phosphorylation in CAF during tumor progression, highlighting the need to inhibit Akt function in both tumor cells and cells that comprise the tumor microenvironment. Cancer Res; 75(5); 813-23. Ó2015 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Akt–Girdin Signaling in Cancer-Associated Fibroblasts Contributes to Tumor Progression

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Likewise, signaling by PDGFR-β in CAFs has been demonstrated to promote metastasis of colorectal cancer [46,47]. Functionally, CAF PDGFR-β and PC PDGFR-β promote the generation of a high interstitial fluid pressure in tumors, thus impairing the delivery of therapeutic agents [48][49][50].…”

Section: Platelet Derived Growth Factor Receptor-βmentioning

confidence: 99%

Functional subsets of mesenchymal cell types in the tumor microenvironment

Cortez

Roswall

Pietras

2014

Seminars in Cancer Biology

View full text Add to dashboard Cite

In the field of tumor biology, increasing attention is now focused on the complex interactions between various constituent cell types within the tumor microenvironment as being functionally important for the etiology of the disease. The detailed description of tumor-promoting properties of cancer-associated fibroblasts, endothelial cells, pericytes, and immune cells, introduces novel potential drug targets for improved cancer treatments, as well as a rationale for exploring the tumor stroma as a previously unchartered source for prognostic or predictive biomarkers.However, recent work highlights the fact that cellular identity is perhaps too broadly defined and that subdivision of each cell type may reveal functionally distinct subsets of cells. Here, we will review our current understanding of the diversity of different subsets of mesenchymal cells, i.e., cancer-associated fibroblasts and pericytes, residing within the tumor parenchyma.

show abstract

“…29 In addition, overexpression of STC2 correlates with lymph node metastasis and venous invasion in gastric cancer, 23 and increases motility and invasiveness of fibroblast morphology, 30 but knockdown of STC2 under hypoxic conditions reverses the migration of colon cancer. 30 However, few studies show that STC1 inhibits cell proliferation and invasion and knockdown of STC1 facilitates cell growth, migration, and invasion in cervical cancer.…”

Section: Invasion and Metastasismentioning

confidence: 99%

Evolution and functions of stanniocalcins in cancer

Zhang

et al. 2015

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

Corpuscles of stannius (CS), a small endocrine gland located on the ventral surface of the kidneys of bony fishes, is extracted to purify stanniocalcins (STCs), which inhibit whole-body Ca2+ influx in the whole body, especially in gill and gut. CSs were first considered to be unique endocrine glands in fish, but were further verified to appear in mammalians, indicating that STCs may function in mammalians as calcium regulation, oxidative stress, anti-inflammation, angiogenesis, ischemia reperfusion, etc. Moreover, the relationship and molecular mechanisms of STC1 expression in cancer become the studied focus and front field. STC2 as a STC1 homolog is identified by searching for related sequences in expressed sequence tag databases. Although mammalian STC1 and STC2 are not expressed ubiquitously in tissue cells, they are distributed in a wide variety of tissues and organs including cancer, and play an important role in tumor development and progression. Molecular structureSTC is present in all vertebrates as two isoforms, STC1 and STC2, encoded by separate genes. 1 STC1, originally described as an antihypercalcemic hormone in fish, is highly expressed in differentiated mammalian neurons. STC1 adopts a dimeric and slightly elongated structure with a high content of alpha-helices. 2 STC2, a homolog of STC1, is a 56kD glycoprotein hormone that confers calcitonin-like activity. A widespread distribution of SCT1 and STC2 is present in mammals and fish, in which the highest amount of STC mRNA is in the heart but lower amounts are found in the neural complex, branchial basket, and endostyle. STCs have a conserved pattern of 10 cysteines in Evolution and functions of stanniocalcins in cancer S-J Chu, 1 J Zhang, 2 R Zhang, 2 W-W Lu 2 and J-S Zhu 2 Abstract Stanniocalcin (STC), first isolated from the corpuscles of stannius of teleost fishes, was originally known for its regulation on calcium/phosphate transport. Increasing evidence demonstrates that STCs display the important function in some physiological and pathological behaviors such as calcium regulation, oxidative stress, anti-inflammation, angiogenesis, ischemia reperfusion, nerve diseases, etc. Moreover, STCs are implicated in the development and progression of multiple malignancies through promoting cell growth, proliferation, invasion, metastasis, and apoptotic escape. Some studies have shown that NF-κB upregulates STC expression, thereby activating the downstream HIF-1/ERK1/2 signaling pathway, enhancing the transcriptional activity of tumor-related factors (MMP-2/9, cyclinD1, Bcl-2, N-cadherin, etc) and contributing to tumorigenesis. Here, this brief review describes recent progress of STCs in mammalians, focused mainly on their critical functions in cancer.

show abstract

STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer

Cited by 146 publications

References 38 publications

Akt–Girdin Signaling in Cancer-Associated Fibroblasts Contributes to Tumor Progression

Akt–Girdin Signaling in Cancer-Associated Fibroblasts Contributes to Tumor Progression

Functional subsets of mesenchymal cell types in the tumor microenvironment

Evolution and functions of stanniocalcins in cancer

Contact Info

Product

Resources

About