Regulation of periostin expression by Notch signaling in hepatocytes and liver cancer cell lines

Kongkavitoon, Pornrat; Butta, Patcharavadee; Sanpavat, Anapat; Bhattarakosol, Pattarasinee; Tangtanatakul, Pattarin; Wongprom, Benjawan; Tangkijvanich, Pisit; Hirankarn, Nattiya; Palaga, Tanapat

doi:10.1016/j.bbrc.2018.10.144

Cited by 15 publications

(11 citation statements)

References 20 publications

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“…However, HCC stroma seems to express higher POSTN than substantial tissue. Our results are consistent with some previous studies of HCC [ 16 , 39 ]. These data indicated that, apart from its roles in EMT confirmed in this study and plenty of other reports, POSTN may have other roles related to ECM.…”

Section: Discussionsupporting

confidence: 94%

“…It also has essential effects on collagen fibrillogenesis, cell adhesion, wound healing, and EMT [ 15 ]. Aberrant POSTN expression has been found in multitude tumor entities, including head and neck, lung, neuroblastoma, breast, and colorectal cancers and HCC, for its roles in cell survival, EMT, angiogenesis, and tumor microenvironment construction [ 13 , 14 , 16 ]. For example, pancreatic cancer cells stimulate stromal cells to secrete POSTN, which induces tumor desmoplasia and EMT to promote tumor progression [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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miR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma

Chen

Zhang³

et al. 2020

BioMed Research International

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Background. The asymptomatic onset, frequent recurrence, and poor prognosis of hepatocellular carcinoma (HCC) prompted us to identify new therapeutic targets or predictive markers of HCC diagnosis or prognosis. Methods. In this study, bioinformatics analysis was used to screen for target miRNAs from the open-access TCGA database. Transwell assays, Western blotting, and qRT-PCR analyses were used to detect cellular functions and gene expression in HCC cells and samples. A nude mouse tumorigenesis model was established to facilitate the observation of HCC progression. Other assays included luciferase reporter assays, IHC, and survival analysis. Results. We found that the identified miR-876 from TCGA was expressed at low levels in HCC cell lines and that low miR-876 expression was corrected with liver cirrhosis, tumor thrombus, and TNM stage. Further research revealed that miR-876 regulated cell invasion, EMT, and collagen expression by targeting POSTN expression. miR-876 and POSTN were inversely correlated in HCC samples and associated with EMT status and liver fibrosis in clinical HCC tissues. miR-876 inhibited the liver cancer progression in in vivo animal assays. Finally, both miR-876 and POSTN were risk factors for HCC survival, and HCC patients with combined low miR-876 and high POSTN expression had worse prognosis. Conclusions. miR-876 inhibited HCC EMT and fibrosis by targeting POSTN, thus affecting HCC progression and prognosis. miR-876 and POSTN may be useful therapeutic targets or prognostic markers of HCC.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

miR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma

Chen

Zhang³

et al. 2020

BioMed Research International

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“…A major class of agents targeting the Notch pathway is GSIs, which are the first Notch inhibitors to enter clinical studies[81]. Favorable tissue penetration, low cost, ease of administration, and potential pan-Notch inhibitory activity are the main advantages of GSIs[82,83]. However, the toxicity of these agents, especially the serious toxicity in the gastrointestinal tract, may affect the further development of this class of inhibitors[84].…”

Section: Csc Signaling Pathways and Inhibitorsmentioning

confidence: 99%

Targeting cancer stem cells in drug discovery: Current state and future perspectives

Zhou

Sun

et al. 2019

WJSC

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In recent decades, cancer stem cells (CSCs) have been increasingly identified in many malignancies. CSC-related signaling pathways and their functions provide new strategies for treating cancer. The aberrant activation of related signaling pathways ( e.g ., Wnt, Notch, and Hedgehog pathways) has been linked to multiple types of malignant tumors, which makes these pathways attractive targets for cancer therapy. CSCs display many characteristic features, such as self-renewal, differentiation, high tumorigenicity, and drug resistance. Therefore, there is an urgent need to develop new therapeutic strategies to target these pathways to control stem cell replication, survival, and differentiation. Notable crosstalk occurs among different signaling pathways and potentially leads to compensatory escape. Therefore, multitarget inhibitors will be one of the main methods to overcome the drug resistance of CSCs. Many small molecule inhibitors of components of signaling pathways in CSCs have entered clinical trials, and some inhibitors, such as vismodegib, sonidegib, and glasdegib, have been approved. Tumor cells are susceptible to sonidegib and vismodegib resistance due to mutations in the Smo protein. The signal transducers and activators of transcription 3 (STAT3) inhibitor BBI608 is being evaluated in a phase III trial for a variety of cancers. Structural derivatives of BBI608 are the main focus of STAT3 inhibitor development, which is another strategy for CSC therapy. In addition to the potential pharmacological inhibitors targeting CSC-related signaling pathways, other methods of targeting CSCs are available, such as nano-drug delivery systems, mitochondrion targeting, autophagy, hyperthermia, immunotherapy, and CSC microenvironment targeting. In addition, we summarize the latest advances in the clinical development of agents targeting CSC-related signaling pathways and other methods of targeting CSCs.

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“…Their merit includes pan-Notch inhibitory activity, favorable tissue distribution, oral administration, and low cost (Andersson and Lendahl, 2014;Kongkavitoon et al, 2018). However, they show gastrointestinal tract toxicity, prompting cautious usage, and restraining further development for clinical applications (Takebe et al, 2014).…”

Section: Therapeutic Targeting Of Notch Hedgehog and Wnt Signaling Pathways: Clinical Update And Recent Development Of The Inhibitorsmentioning

confidence: 99%

The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies

Kumar

Vashishta

Kong

et al. 2021

Front. Cell Dev. Biol.

107

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Resistance to therapy is the major hurdle in the current cancer management. Cancer cells often rewire their cellular process to alternate mechanisms to resist the deleterious effect mounted by different therapeutic approaches. The major signaling pathways involved in the developmental process, such as Notch, Hedgehog, and Wnt, play a vital role in development, tumorigenesis, and also in the resistance to the various anticancer therapies. Understanding how cancer utilizes these developmental pathways in acquiring the resistance to the multi-therapeutic approach cancer can give rise to a new insight of the anti-therapy resistance mechanisms, which can be explored for the development of a novel therapeutic approach. We present a brief overview of Notch, Hedgehog, and Wnt signaling pathways in cancer and its role in providing resistance to various cancer treatment modalities such as chemotherapy, radiotherapy, molecular targeted therapy, and immunotherapy. Understanding the importance of these molecular networks will provide a rational basis for novel and safer combined anticancer therapeutic approaches for the improvement of cancer treatment by overcoming drug resistance.

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Regulation of periostin expression by Notch signaling in hepatocytes and liver cancer cell lines

Cited by 15 publications

References 20 publications

miR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma

miR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma

Targeting cancer stem cells in drug discovery: Current state and future perspectives

The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies

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