Fendiline inhibits proliferation and invasion of pancreatic cancer cells by interfering with ADAM10 activation and β-catenin signaling

Woods, Neha Kabra; Treviño, José G.; Coppola, Domenico; Chellappan, Srikumar; Yang, Shengyu; Padmanabhan, Jaya

doi:10.18632/oncotarget.5933

Cited by 39 publications

(40 citation statements)

References 71 publications

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“…[81] The arbitrary use of Ca 2+channel blockers for cancer prevention and therapy is equally ill advised. While preclinical investigations have identified cancer preventive effects of Ca 2+ -channel blockers in a large spectrum of cancers, [82][83][84] these agents not only suppress molecular targets studied in these cancers but additionally inhibit the release of Nor and Epi from sympathetic nerves, [85] thereby suppressing the beta-adrenergic receptor-mediated formation of cAMP. In turn, this effect can selectively promote the development and progression of cancers in which cAMP has tumor suppressor function.…”

Section: Discussionmentioning

confidence: 99%

A new twist to neurotransmitter receptors and cancer

Schüller¹

2017

JCMT

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Section: Discussionmentioning

confidence: 99%

A new twist to neurotransmitter receptors and cancer

Schüller¹

2017

JCMT

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“…Lymphoma [103], esophagus [104] colorectal [105], uveal melanoma [106], pancreas [107,108], breast [21,109,110], glioblastoma [111,112], nasopharyngeal [81], hepatocellular [113,114] tongue [115],…”

Section: Tumor Growth and Survivalmentioning

confidence: 99%

“…bladder [82], oral [116], pituitary gland [85], NSCLC [117] Immune evasion [103,104,109,110,112,114], chemoresistance [82,105,112,114], growth [81,105,107,113], metastasis [21,81,85,106,107,113,[115][116][117] In vitro: [21,81,82,85,[103][104][105]107,108,110,112,[115][116][117],…”

Section: Tumor Growth and Survivalmentioning

confidence: 99%

ADAM protein family – its role in tumorigenesis, mechanisms of chemoresistance and potential as diagnostic and prognostic factors

Zadka

Kulus

Piątek

2018

neo

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ADAMs are a family of transmembrane proteins described for the first time in the 1990's. ADAMs is an abbreviation of "A Disintegrin and Metallo-proteinases". Their earliest known role was involvement in gamete fusion, and their adhesion properties in intercellular interactions also suggested involvement in tumor biology. Further research emphasized the importance of ADAM proteins in the regulation of neoplastic processes due to their influence on adhesion, cell migration, proteolysis and cell signaling. Variable ADAM expression in cancer and normal tissue was the basis for considering these proteins as diagnostic markers. Recent numerous studies have been published suggesting the prognostic value of this protein family members. The ADAMs transmembrane proteins regulate processes associated with carcinogenesis and neoplastic progression, including immune response evasion, growth induction and metastasis. Proteolysis and shedding of membrane proteins and binding integrins by ADAMs lead to the activation of numerous growth factors, changes in the extracellular matrix, adhesion proteins and angiogenesis. ADAMs potential as prognostic and diagnostic markers in cancer treatment is a particularly interesting issue and has great practical significance. There are many new studies concerning ADAMs' roles in carcinogenesis, but there are no recent reviews of the latest developments in this field. The aim of this systematic review is to analyze the results of studies published on ADAMs in the last 5 years, to present their roles in neoplasm pathogenesis and their potential utility in clinical oncology.

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“…12 We recently reported that ADAM10 inhibition significantly reduces β-catenin-target gene expression, which included cyclin D1, CD44, and c-myc. 18 Another interesting finding is that β-catenin nuclear signaling can induce transcription of ADAM10, thereby playing a feed forward role in the vicious cycle of tumor promotion. Thus, inhibition of ADAM10 protease could be a promising strategy for the prevention of cancer cell migration and invasion and overcoming drug resistance.…”

Section: Editorialmentioning

confidence: 99%

“…Studies have implicated that calcium influx activates ADAM10 and we found that calcium channel inhibitors interfere with ADAM10 cellular distribution at the membrane and promote formation of tight cell-adhesions. 18 Additional studies will enable elucidation of calcium-dependent or independent mechanisms that activate ADAM10. An understanding of the specific role of ADAM10 in PDAC progression or metastasis would enable us to determine if targeted inhibition of ADAM10 is a viable option for overcoming drug resistance and metastasis associated with PDAC.…”

Section: Editorialmentioning

confidence: 99%

ADAM10 Proteases and Pancreatic Cancer

Padmanabhan¹

2016

Pancreas Open J

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ADAM10 Proteases and Pancreatic CancerPage e8 EditorialPancreatic ductal adenocarcinoma (PDAC) is the 4 th leading cause of cancer-related deaths in the United States and is expected to rise to the second rank by 2020. 1 The survival rate of PDAC is estimated at less than 5% and the high mortality rate is attributed to the asymptomatic progression and aggressive nature of the tumor, which exhibit locally advanced or metastatic disease at the time of diagnosis. Majority of the pancreatic cancers are PDACs and are characterized by a fibrotic tumor stroma.The nucleoside analog Gemcitabine is the standard therapy used for treatment of PDAC but it shows only marginal therapeutic benefit.2,3 The limited accessibility of the drugs to the tumors is one of the major issues with PDAC, given the dense, highly fibrotic nature of the stroma. Tumor stroma comprises of Extracellular matrix (ECM) proteins, growth factors such as fibronectin and collagen, stromal fibroblasts, stellate cells, immune cells, and blood vessels. 4 The strong desmoplastic tumor stroma inhibits transvascular transport of drugs to the tumors, and therefore the tumors continue to grow and metastasize. Though the newly developed combinatorial therapies such as Nab-Paclitaxel (colloidal suspension of paclitaxel and human serum albumin) and FOLFIRINOX (combination of oxaliplatin, 5-FU, lucovorin and irinotecan) have shown significant improvement in survival in patients with metastatic cancer, they are associated with severe toxicity issues, and therefore additional strategies are being developed to effectively treat PDAC. 5,6 It is known that matrix-degrading enzymes affect cell adhesion and migration. Several transmembrane proteins that are involved in cell adhesion are cleaved by matrix degrading enzymes like matrix metalloproteinases, allowing detachment, migration and metastasis of cancer cells. Among the proteases, A Disintegrin And Metalloprotease (ADAM) family member ADAM10 has recently gained considerable attention for its role in tumor progression and metastasis. 7,8 The metalloprotease domain of ADAM10 is involved in proteolysis and ectodomain shedding of extracellular matrix-associated proteins whereas its disintegrin and cysteine rich domains are known to have adhesive activities.9 Proteins such as cadherins, CD44, Notch, Ephrin B1, amyloid precursor protein, and the chemokine CXCL16 are a few examples, whose ectodomain release contributes to migration and invasion of cancer cells. [10][11][12][13] Recent studies by others and us have shown that ADAM10 inhibition or down-regulation enhances the chemosensitivity of PDAC cells to gemcitabine and prevents their anchorage independent growth and migration. [13][14][15][16] PDACs over express ADAM10, and down-regulation of ADAM10 in PDAC cells have shown to significantly reduce the secreted levels of the soluble ectodomains of its substrates. We recently demonstrated that ADAM10 inhibition enhances cell-cell adhesion and formation of cadherin positive tight adherens junctions, indicating that activ...

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Fendiline inhibits proliferation and invasion of pancreatic cancer cells by interfering with ADAM10 activation and β-catenin signaling

Cited by 39 publications

References 71 publications

A new twist to neurotransmitter receptors and cancer

A new twist to neurotransmitter receptors and cancer

ADAM protein family – its role in tumorigenesis, mechanisms of chemoresistance and potential as diagnostic and prognostic factors

ADAM10 Proteases and Pancreatic Cancer

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