<scp>SPOCK</scp>1 promotes the invasion and metastasis of gastric cancer through Slug‐induced epithelial‐mesenchymal transition

Chen, Dehu; Zhou, Hai-Hua; Liu, Guiyuan; Zhao, Yi; Cao, Gan; Liu, Qinghong

doi:10.1111/jcmm.13357

Cited by 57 publications

(57 citation statements)

References 26 publications

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“…reported that SPOCK1 was involved in slug-induced EMT and promoted cell invasion and metastasis, which high expression was also a prognostic factor for poor survival in gastric cancer (10). Results in this study documented that SPOCK1 was highly expressed in BC cells and clinical specimens relative to normal ones, which were paralleled with Oncomine, HPA and Ualcan databases.…”

Section: Discussionsupporting

confidence: 69%

SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway

Zhang

et al. 2019

Preprint

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SPOCK1 is highly expressed in many types of cancer, which has been recognized as a promoter of cancer progression, while its regulatory mechanism remains to be clear in breast cancer (BC). This study aimed to explore the precise function of SPOCK1 in BC progression and the mechanism by which SPOCK1 was involved in cell proliferation and epithelial-mesenchymal transition (EMT).Immunohistochemistry (IHC) and database analysis displayed that high expression of SPOCK1 was positively associated with histological grade, lymph node metastasis (LN) and poor clinical prognosis in BC. A series of assays both in vitro and in vivo elucidated that altering SPOCK1 level led to distinctly changes in BC cell proliferation and metastasis. Investigations of potential mechanisms revealed that SPOCK1 interacted with SIX1 could enhance cell proliferation, cell cycle and EMT process by activating the AKT/mTOR pathway, whereas inhibition of AKT/mTOR pathway or depletion of SIX1 reversed the effects of SPOCK1 overexpression.Furthermore, SPOCK1 and SIX1 were highly expressed in BC and might indicate poor prognoses. Altogether, SPOCK1/SIX1 promoted BC progression by activating AKT/mTOR pathway to accelerate cell proliferation and metastasis in BC, and SPOCK1/SIX1 might be promising clinical therapeutic targets to prevent BC progression. IMPORTANCE:The incidence of BC is alarmingly high and many patients initially diagnosed without detectable metastases will eventually develop metastatic lesions. The occurrence of metastasis is responsible for the death of many patients, which also represents a big challenge for researchers to improve the survival rates of BC patients.Hence the scientific community pays more attention on cancer targeted therapy. This research is significant for identifying the underlying mechanisms and capabilities of SPOCK1-induced BC activities, which will greatly apply novel targets and new treatment strategies for clinicians, leading to broader biomedical impacts. KEYWORDS: SPOCK1; SIX1; EMT; Breast cancer; AKT/mTOR signaling pathwayBreast cancer (BC), the most frequently diagnosed lethal gynecologic malignancy in women worldwide (1), which is an increasing concern because of its rising incidence. Despite major advances in BC therapy, the prognosis for most patients would be significantly worse once spread metastasized occurs (2). Metastasis is the mainspring for most patient death and represents the fundamental challenge of the clinical treatment for the patients with BC. The initiation and metastasis of BC are intricate processes, which triggered by multiple genes and intracellular signal transduction cross-talks. Thus, looking for valid molecular hallmarks and understanding the mechanisms of BC initiation and metastasis process are urged to put on the agenda. Sparc/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1), is also known as TIC1; SPOCK; TESTICAN, belongs to multidomain testicular proteoglycan family (3). This protein family includes SPARC, TESTICAN-2, and TESTICAN-3, which are associated with ...

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Section: Discussionsupporting

confidence: 69%

SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway

Zhang

et al. 2019

Preprint

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“…CLIP2 involves the TNF-α singling pathway 25 to play an important role in gastric tumorigenesis 26 . SPOCK1, a representative target www.nature.com/scientificreports www.nature.com/scientificreports/ gene of miR-375, has been demonstrated to facilitate metastasis in certain types of cancer and to promote GC invasion and metastasis through a Slug-dependent mechanism 27 . PENK and ADAMTS16 are representative DEGs of miR-1260.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Kim

Jang

Heo

et al. 2020

Sci Rep

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Understanding cancer-prone environments is important to efficiently detect and prevent cancers. The associations between miRNA and cancer-prone environments are still largely unknown in gastric cancer (GC). Six miRNAs that are differentially expressed during gastric carcinogenesis were selected, and quantitative real-time pcR was performed in an independent training set (fresh non-tumor and tumor samples from 18 GC patients) and validation sets (set 1 with formalin-fixed paraffin-embedded non-tumor and tumor samples from 19 solitary GC and set 2 with 37 multiple GC patients). The results were compared with those of 37 gastric mucosa from 20 healthy volunteers. The expression levels of miR-26a, miR-375, and miR-1260 in gastric mucosa from healthy volunteers were statistically higher than that of non-tumorous gastric mucosa located 3 cm apart from the GC in the training set (miR-26a, P < 0.0001; miR-375, P = 0.0049; miR-1260, P = 0.0172), validation set 1 (miR-26a and miR-375, P < 0.0001; miR-1260, P = 0.0008), and validation set 2 (miR-26a, miR-375, and miR-1260, P < 0.0001). And a combination of miR-26a and miR-1260 showed the highest area under the curve value of 0.89. miRNAs are differentially expressed in non-neoplastic gastric mucosa and can be used as a biomarker to predict cancer-prone environments.

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“…EMT is tightly regulated by TFs. Apart from the prominent TFs, such as Slug [ 17 ], Snail [ 18 ], Twist1/2 [ 19 , 20 ], FOXQ1 [ 21 ] and ZEB1/2 [ 22 – 25 ] in GC, there are emerging novel TFs that have also been found to regulate EMT. For example, runt-related TF 3 (RUNX3), which has a role in suppressing EMT through the TGF-β-activated SMAD pathway, has been observed to be frequently downregulated [ 26 , 27 ].…”

Section: Emtmentioning

confidence: 99%

Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer

Wong

et al. 2018

Oncogene

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The term metastasis is widely used to describe the endpoint of the process by which tumour cells spread from the primary location to an anatomically distant site. Achieving successful dissemination is dependent not only on the molecular alterations of the cancer cells themselves, but also on the microenvironment through which they encounter. Here, we reviewed the molecular alterations of metastatic gastric cancer (GC) as it reflects a large proportion of GC patients currently seen in clinic. We hope that further exploration and understanding of the multistep metastatic cascade will yield novel therapeutic targets that will lead to better patient outcomes.

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SPOCK1 promotes the invasion and metastasis of gastric cancer through Slug‐induced epithelial‐mesenchymal transition

Cited by 57 publications

References 26 publications

SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway

SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer

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