GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling

Khanna, Puja; Lee, Joan Shuying; Sereemaspun, Amornpun; Lee, Haeryun; Baeg, Gyeong Hun

doi:10.1038/s41598-018-27864-6

Cited by 44 publications

(33 citation statements)

References 60 publications

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“…The previously mentioned Wwox can inhibit breast cancer metastasis by preventing receptor binding [35]. Furthermore, Kim et al have demonstrated that Mesodermspecific transcript (MEST) induces Twist expression by activating the JAK/STAT3 signaling pathway [51], whereas Khanna et al have shown the inhibition of GRAM domain-containing protein 1B (GRAMD1B) in breast cancer migration via the suppression of the JAK/ STAT3 and protein kinase B (Akt) pathway [52]. Instead of classical ligand/receptor binding in the plasma membrane for STAT3 activation, a new pathway is found in which OSM/SMAD3 could also activate STAT3 and mediate Snail expression and promote epithelialmesenchymal transition (EMT) in breast cancer, indicating a distinct route of STAT3 activation through cytoplasmic molecules and endogenous signaling [53].…”

Section: The Role Of Stat3 In Breast Cancer Metastasismentioning

confidence: 99%

Role of STAT3 signaling pathway in breast cancer

2020

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Breast cancer has grown to be the second leading cause of cancer-related deaths in women. Only a few treatment options are available for breast cancer due to the widespread occurrence of chemoresistance, which emphasizes the need to discover and develop new methods to treat this disease. Signal transducer and activator of transcription 3 (STAT3) is an early tumor diagnostic marker and is known to promote breast cancer malignancy. Recent clinical and preclinical data indicate the involvement of overexpressed and constitutively activated STAT3 in the progression, proliferation, metastasis and chemoresistance of breast cancer. Moreover, new pathways comprised of upstream regulators and downstream targets of STAT3 have been discovered. In addition, small molecule inhibitors targeting STAT3 activation have been found to be efficient for therapeutic treatment of breast cancer. This systematic review discusses the advances in the discovery of the STAT3 pathways and drugs targeting STAT3 in breast cancer.

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Section: The Role Of Stat3 In Breast Cancer Metastasismentioning

confidence: 99%

Role of STAT3 signaling pathway in breast cancer

2020

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“…The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is implicated in the development and progression of many cancers [1,2] . Hyperactivation of STAT transcription factors, has been reported in both hematologic malignancies and solid tumors, including cancers of the breast, lung, liver, head and neck, and stomach, among others [3][4][5][6][7][8] . For many of these cancers, increased activation of the JAK/STAT signaling pathway is associated with a worse prognosis, including increased recurrence and reduced overall survival [1,9,10] .…”

Section: Introductionmentioning

confidence: 99%

Targeting the JAK/STAT pathway in solid tumors

Qureshy¹,

Johnson²,

Grandis³

2020

JCMT

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Aberrant activation of signal transducer and activator of transcription (STAT) proteins is associated with the development and progression of solid tumors. However, as transcription factors, these proteins are difficult to target directly. In this review, we summarize the role of targeting Janus kinases (JAKs), upstream activators of STATs, as a strategy for decreasing STAT activation in solid tumors. Preclinical studies in solid tumor cell line models show that JAK inhibitors decrease STAT activation, cell proliferation, and cell survival; in in vivo models, they also inhibit tumor growth. JAK inhibitors, particularly the JAK1/2 inhibitor ruxolitinib, sensitize cell lines and murine models to chemotherapy, immunotherapy, and oncolytic viral therapy. Ten JAK inhibitors have been or are actively being tested in clinical trials as monotherapy or in combination with other agents in patients with solid tumors; two of these inhibitors are already Food and Drug Administration (FDA) approved for the treatment of myeloproliferative disorders and rheumatoid arthritis, making them attractive agents for use in patients with solid tumors as they are known to be well-tolerated. Four JAK inhibitors (two of which are FDA approved for other indications) have exhibited promising anti-cancer effects in preclinical studies; however, clinical studies specifically assessing their activity against the JAK/STAT pathway in solid tumors have not yet been conducted. In summary, JAK inhibition is a viable option for targeting the JAK/STAT pathway in solid tumors and merits further testing in clinical trials.

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“…Previous studies found that activation of PI3K/AKT signaling increases MGP expression (Mirsaidi et al , 2017; Ponnusamy et al , 2018). Although the crosstalk of JAK2/STAT5 signaling and PI3K/AKT signaling has been reported (Britschgi et al , 2012; Khanna et al , 2018), the underlying mechanisms remain largely unknown. Our study used multiple lines of evidences supporting MGP as a novel transcriptional co‐activator of STAT5.…”

Section: Discussionmentioning

confidence: 99%

Intracellular matrix Gla protein promotes tumor progression by activating JAK2/STAT5 signaling in gastric cancer

Wang

Chen

et al. 2020

Molecular Oncology

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Matrix Gla protein (MGP) has been widely reported as an extracellular matrix protein with abnormal expression in various types of cancer. However, the function of intracellular MGP in gastric cancer (GC) cells remains largely unknown. Here, we demonstrated aberrantly high expression of intracellular MGP in GC as compared to adjacent normal tissues by immunohistochemistry. Moreover, The Cancer Genome Atlas (TCGA) dataset analysis suggested a positive correlation between MGP overexpression and unfavorable prognosis. MGP silencing reduced cell proliferation, migration, invasion, and survival in GC cell lines. Gene set enrichment analysis of TCGA dataset indicated significant enrichment of the IL2-STAT5 signaling in MGP-high GC patients. Immunofluorescence staining and immunoprecipitation showed that MGP binds to p-STAT5 in the nuclei of GC cells. Furthermore, ChIP-qPCR and luciferase reporter assays indicated that MGP acts as a transcriptional co-activator through the enhancement of STAT5 binding to target gene promoters. Use of STAT5 inhibitor revealed that the oncogenic functions of intracellular MGP mainly depend on the JAK2/STAT5 signaling pathway. Taken together, our results indicate that intracellular MGP promotes proliferation and survival of GC cells by acting as a transcriptional co-activator of STAT5. The detected aberrant, high MGP expression in GC tissues highlights MGP as a potential new prognostic biomarker in patients with GC.

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GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling

Cited by 44 publications

References 60 publications

Role of STAT3 signaling pathway in breast cancer

Role of STAT3 signaling pathway in breast cancer

Targeting the JAK/STAT pathway in solid tumors

Intracellular matrix Gla protein promotes tumor progression by activating JAK2/STAT5 signaling in gastric cancer

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