Bosutinib inhibits migration and invasion via ack1 in kras mutant non-small cell lung cancer

Tan, Daniel S.W.; Haaland, Benjamin; Gan, Jia; Tham, Su Chin; Sinha, Indrajit; Tan, Eng Huat; Lim, Kiat Hon; Takano, Angela; Krisna, Sai Sakktee; Thu, Minn Minn Myint; Liew, Hoe Peng; Ullrich, Axel; Lim, Wan‐Teck; Chua, Boon Tin

doi:10.1186/1476-4598-13-13

Cited by 48 publications

(52 citation statements)

References 31 publications

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“…It was reported in many studies that miR-940 was highly expressed in normal tissues compared with tumors, and miR-940 was shown to inhibit the migratory and invasive potential of cancer cells by suppressing CXCR2 [59], MIEN1 [58], MyD88 [57], Nestin [56], and ZNF24 [54]. Moreover, the Estrogen-Related Receptor Gamma (ESRRG) was targeted by miR-940, and suppression of ESRRG inhibited hepatocellular carcinoma cell lines growth and induced cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs

Rashed

Kanlikilicer²,

Rodríguez-Aguayo³

et al. 2017

Oncotarget

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Exosomes have emerged as important mediators of diverse biological functions including tumor suppression, tumor progression, invasion, immune escape and cell-to-cell communication, through the release of molecules such as mRNAs, miRNAs, and proteins. Here, we identified differentially expressed exosomal miRNAs between normal epithelial ovarian cell line and both resistant and sensitive ovarian cancer (OC) cell lines. We found miR-940 as abundant in exosomes from SKOV3-IP1, HeyA8, and HeyA8-MDR cells. The high expression of miR-940 is associated with better survival in patients with ovarian serous cystadenocarcinoma. Ectopic expression of miR-940 inhibited proliferation, colony formation, invasion, and migration and triggered G0/G1 cell cycle arrest and apoptosis in OC cells. Overexpression of miR-940 also inhibited tumor cell growth in vivo. We showed that proto-oncogene tyrosine-protein kinase (SRC) is directly targeted by miR-940 and that miR-940 inhibited SRC expression at mRNA and protein levels. Following this inhibition, the expression of proteins downstream of SRC, such as FAK, paxillin and Akt was also reduced. Collectively, our results suggest that OC cells secrete the tumor-suppressive miR-940 into the extracellular environment via exosomes, to maintain their invasiveness and tumorigenic phenotype.

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Section: Discussionmentioning

confidence: 99%

Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs

Rashed

Kanlikilicer²,

Rodríguez-Aguayo³

et al. 2017

Oncotarget

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“…Among all the glycolytic enzymes, LDH is of great importance to maintain high glycolysis rate. And LDHA is reported to be up-regulated in many cancers [16, 17, 19–21, 23]. …”

Section: Discussionmentioning

confidence: 99%

miR-200b is a key regulator of tumor progression and metabolism targeting lactate dehydrogenase A in human malignant glioma

Jiang

Luo

et al. 2016

Oncotarget

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Lactate dehydrogenase A (LDHA) is involved in various cancers. In this study, we investigated the expression and function of LDHA in glioma. We found that LDHA was up-regulated in glioma samples. Furthermore, we found that overexpression of LDHA promoted proliferation, invasion and glycolysis in glioma cells. Luciferase reporter assays confirmed that LDHA was a direct target of miR-200b. miR-200b was found to be down-regulated in glioma samples, which was inversely correlated with LDHA expression. Repression of LDHA by miR-200b suppressed the glycolysis, cell proliferation and invasion of glioma cells. These results provide evidence that miR-200b acts as a tumor suppressor in glioma through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-200b could be a potential therapeutic strategy in glioma.

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“…ACK1, an intracellular tyrosine kinase, is considered to be implicated in regulating multiple aspects of tumor progression (13,16). Several studies have indicated that ACK1 overexpression is commonly observed in human cancers including lung and prostate cancer (27,33). Furthermore, it has been demonstrated that ACK1 can promote tumor growth via regulating pro-survival molecules such as AKT and AR in various cancers (26,31,33).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have implicated ACK1 amplification and high-expression in carcinogenesis of multiple tissue types such as lung, breast and prostate (27)(28)(29). Overexpression level of ACK1 correlates with tumor invasion and migration in renal and pancreatic cancers (30,31).…”

Section: Introductionmentioning

confidence: 99%

ACK1 promotes hepatocellular carcinoma progression via downregulating WWOX and activating AKT signaling

Xie

Zen

Wang

et al. 2015

International Journal of Oncology

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Abstract. Several studies have revealed that ACK1 is upregulated in various cancers and promotes tumor progression. However, the role and mechanism of ACK1 in hepatocellular carcinoma (HCC) remains unknown. In this study, the expression of ACK1 was assessed in several cell lines and 150 pairs of HCC and adjacent noncancerous liver tissues. The protein expression of p-ACK1 and WWOX were detected by immunohistochemistry to evaluate their correlation with ACK1. Flow cytometry, caspase 3/7 activity assay, BrdU cell proliferation assay, MTT assay and Transwell assay were used to detect apoptosis, proliferation, invasion and migration of HCC cells. The regulatory effect of ACK1 on WWOX, AKT, p-AKT, MMP2 and MMP9 in HCC cells was confirmed by immuno blotting. We found that ACK1 was more highly expressed in HCC tissues than in non-HCC tissues, and over expression of ACK1 was correlated with clinicopathological features of poor prognosis. Clinical analysis demonstrated that ACK1 is an independent prognostic marker for predicting overall survival and disease-free survival of HCC patients. Pearson's correlation coefficient analysis indicated that ACK1 was positively associated with p-ACK1 and was negatively associated with WWOX expression. In vitro studies showed that knockdown of ACK1 promoted HCC cell apoptosis and repressed HCC cells invasion, migration and proliferation. Furthermore, knockdown of ACK1 resulted in upregulation of WWOX and inactivation of AKT signaling. In this study, we also found that knockdown of ACK1 resulted in the downregulation of MMP2 and MMP9 in HCC. Our results indicate that ACK1 is an independent prognostic marker and promotes HCC progression via downregulating WWOX and activating AKT signaling.

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Bosutinib inhibits migration and invasion via ack1 in kras mutant non-small cell lung cancer

Cited by 48 publications

References 31 publications

Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs

Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs

miR-200b is a key regulator of tumor progression and metabolism targeting lactate dehydrogenase A in human malignant glioma

ACK1 promotes hepatocellular carcinoma progression via downregulating WWOX and activating AKT signaling

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