Liver kinase B1 suppresses metastasis and angiogenesis of lung cancer: involvement of the Shh signaling pathway

Zheng, Guoliang; Song, Kuiyuan; Zhao, Yuwei

doi:10.4149/neo_2018_180820n630

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…In addition, the mRNA and protein levels of E-Ca were dramatically increased, while the expressions of N-Ca and vimentin were significantly decreased in TPC-1 and BCPAP cells with LKB1 overexpression. For the angiogenesis, LKB1 was also found to suppress lung cancer angiogenesis by Shh signaling pathway [20]. Depletion of LKB1 could accelerate the angiogenesis via VEGF [21].…”

Section: Discussionmentioning

confidence: 98%

LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1

Kou¹,

Wang²,

Sun³

et al. 2022

J. Cancer

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Purpose: Liver kinase B1 (LKB1), also known as serine/threonine kinase 11, was considered as a tumor suppressor, which exhibited anti-cancer activity in a variety of cancers. However, the effect of LKB1 in thyroid cancer remains unclear. Methods: In the study, MTT assay, colony formation assay, flow cytometry, western blot analysis, wound healing assay, transwell assays, quantitative real-time PCR, HUVEC migration assay, ELISA assay, tube formation assay and nude mice xenograft were used to investigate the anti-cancer capacity of LKB1 in thyroid cancer in vitro and in vivo. Results: In the present study, we found that the expression of LKB1 was lower in thyroid cancer tissues and cell lines, compared with the adjacent normal tissue and thyroid epithelial cell. After construction of stable clone cells with ectopic LKB1 overexpression, the findings revealed that LKB1 overexpression exerted anti-proliferative and pro-apoptotic property in thyroid cancer TPC-1 and BCPAP cells. In addition, LKB1 overexpression could inhibit migration and invasion, downregulate MMP2 and MMP9 expressions, and reverse EMT in thyroid cancer cells. Furthermore, overexpression of LKB1 attenuated HUVEC recruitment, decreased the expression of VEGFA and inhibited the formation of new vessels in thyroid cancer cells. To validate the underlying mechanism of LKB1 in thyroid cancer, the results showed that LKB1 could positively regulate SIK1 in thyroid cancer TPC-1 and BCPAP cells. Additionally, the SIK1 inhibitor HG-9-91-01 could partially abrogate the anti-proliferative and anti-metastatic effect of LKB1, and reverse MET (mesenchymal-to-epithelial transition) mediated by LKB1 overexpression. Ultimately, the results in vivo revealed that LKB1 overexpression exhibited a strong inhibitory effect of tumorigenicity and presented anti-angiogenic characteristic in nude mice xenograft model. Conclusion: the results demonstrated that LKB1 could inhibit proliferation, metastasis phenotype and angiogenesis, and reverse EMT in thyroid cancer in vitro and vivo via the upregulation of SIK1, suggesting that LKB1 could be considered as a potential therapeutic target for the treatment of thyroid cancer.

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Section: Discussionmentioning

confidence: 98%

LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1

Kou¹,

Wang²,

Sun³

et al. 2022

J. Cancer

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“…The silencing of liver kinase B1 (LKB1) increased levels of VEGF, MMP-2 and MMP-9, enhanced HUVEC activity and migration, and promoted angiogenesis ( 59 ). In addition, after LKB1 silencing, mRNA levels of key molecules in the Shh signaling pathway, such as Shh, Ptch, Smo and Gli1, were increased, and nuclear translocation of Gli1 was enhanced, suggesting that LKB1 can inhibit the Shh signaling pathway, thus inhibiting angiogenesis in lung cancer.…”

Section: Novel Angiogenic Regulators In Lung Cancer Treatmentmentioning

confidence: 99%

Novel Angiogenic Regulators and Anti-Angiogenesis Drugs Targeting Angiogenesis Signaling Pathways: Perspectives for Targeting Angiogenesis in Lung Cancer

Lin

Wang

et al. 2022

Front. Oncol.

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Lung cancer growth is dependent on angiogenesis. In recent years, angiogenesis inhibitors have attracted more and more attention as potential lung cancer treatments. Current anti-angiogenic drugs targeting VEGF or receptor tyrosine kinases mainly inhibit tumor growth by reducing angiogenesis and blocking the energy supply of lung cancer cells. However, these drugs have limited efficiency, raising concerns about limited scope of action and mechanisms of patient resistance to existing drugs. Therefore, current basic research on angiogenic regulators has focused more on screening carcinogenic/anticancer genes, miRNAs, lncRNAs, proteins and other biomolecules capable of regulating the expression of specific targets in angiogenesis signaling pathways. In addition, new uses for existing drugs and new drug delivery systems have received increasing attention. In our article, we analyze the application status and research hotspots of angiogenesis inhibitors in lung cancer treatment as a reference for subsequent mechanistic research and drug development.

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“…In a 2018 study by Xu, Notch signaling pathway inhibitor DAPT was used to negatively regulate the Notch signaling pathway and downregulate RhoA, RhoC, and MMP9, and upregulate RhoB, thereby inhibiting the metastasis and invasion of NSCLC (91). In addition, in 2019, Zheng et al also found that after the Sonic hedgehog (Shh) signaling pathway was transplanted by LKB1, Shh's role in regulating lung cancer metastasis and angiogenesis was also suppressed (92).…”

Section: Signaling Pathways and Lung Cancer Metastasismentioning

confidence: 99%

Research progress on the molecular mechanisms of hepatic metastasis in lung cancer: a narrative review

Ying¹,

Ma²,

Zhang³

et al. 2021

Ann Palliat Med

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The liver is one of the most common sites of metastatic spread of lung cancer, and the process of metastasis is regulated by many factors. A number of genes, including multiple tumor suppressor 1 (mts1), p120 catenin, and CT45A1, increase the possibility of hepatic metastasis in lung cancer, whereas Tip30/ CC3, CUL5, and SOCS3 expression in lung tumors inhibit tumor metastasis. microRNAs (miRNAs), such as miRNA-126, miRNA-338, and miRNA-218, can affect the metastasis of lung cancer cells to the liver. The D114-Notch signaling pathway can inhibit liver metastasis in small cell lung cancer. Serum tumor markers cytokeratin 19 fragment antigen 21-1 and neuron-specific enolase (NSE) are closely related to the risk of hepatic metastasis in lung cancer. Based on previously published literature, we found that the metastasis and invasion of lung cancer to the liver are determined by molecular factors. Therefore, the selective identification and intervention of these erroneous signals can predict early lung cancer metastasis to the liver.In this review article, we describe the mechanisms and influencing factors (genes, signal pathways, chemicals, proteins, miRNAs) of hepatic metastasis in lung cancer. We hope to provide a summary of the evidence for the mechanisms by which related genes or proteins affect the malignancy of liver metastasis from lung cancer so that doctors and researchers can improve treatment options.

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Liver kinase B1 suppresses metastasis and angiogenesis of lung cancer: involvement of the Shh signaling pathway

Cited by 4 publications

References 32 publications

LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1

LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1

Novel Angiogenic Regulators and Anti-Angiogenesis Drugs Targeting Angiogenesis Signaling Pathways: Perspectives for Targeting Angiogenesis in Lung Cancer

Research progress on the molecular mechanisms of hepatic metastasis in lung cancer: a narrative review

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