PKCζ Promotes Breast Cancer Invasion by Regulating Expression of E-cadherin and Zonula Occludens-1 (ZO-1) via NFκB-p65

Paul, Arindam; Danley, Marsha; Saha, Biswarup; Tawfik, Ossama

doi:10.1038/srep12520

Cited by 32 publications

(29 citation statements)

References 112 publications

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“…The Par6-aPKC complex also plays a crucial role in establishing the front-back polarity required for directional cell migration and invasion. PKCζ has been shown to promote invasion and metastasis of breast cancer xenografts in mice by promoting the nuclear localization of NFκB-p65 and suppressing the expression of junctional proteins E-cadherin and ZO1 (Paul et al, 2015). PKCι has also been shown to stimulate cell migration by regulating the trafficking of protease-containing vesicles to the plasma membrane of invadopodia.…”

Section: Atypical Protein Kinase Cs (Apkcs)mentioning

confidence: 99%

Targeting Rho GTPase Signaling Networks in Cancer

Clayton

Ridley

2020

Front. Cell Dev. Biol.

139

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As key regulators of cytoskeletal dynamics, Rho GTPases coordinate a wide range of cellular processes, including cell polarity, cell migration, and cell cycle progression. The adoption of a pro-migratory phenotype enables cancer cells to invade the stroma surrounding the primary tumor and move toward and enter blood or lymphatic vessels. Targeting these early events could reduce the progression to metastatic disease, the leading cause of cancer-related deaths. Rho GTPases play a key role in the formation of dynamic actin-rich membrane protrusions and the turnover of cell-cell and cellextracellular matrix adhesions required for efficient cancer cell invasion. Here, we discuss the roles of Rho GTPases in cancer, their validation as therapeutic targets and the challenges of developing clinically viable Rho GTPase inhibitors. We review other therapeutic targets in the wider Rho GTPase signaling network and focus on the four best characterized effector families: p21-activated kinases (PAKs), Rho-associated protein kinases (ROCKs), atypical protein kinase Cs (aPKCs), and myotonic dystrophy kinase-related Cdc42-binding kinases (MRCKs).

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Section: Atypical Protein Kinase Cs (Apkcs)mentioning

confidence: 99%

Targeting Rho GTPase Signaling Networks in Cancer

Clayton

Ridley

2020

Front. Cell Dev. Biol.

139

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“…PAICS knockdown reduced the mRNA transcripts of these markers ( Figure 6A). The upregulation of E-cadherin and the downregulation of vimentin are indicators of the suppression of the malignant phenotypes of cells [28,29]. To determine if PAICS knockdown had an effect on the levels of E-cadherin and vimentin, these proteins were evaluated by immunoblot analysis.…”

Section: Paics Modulates the Emt In Crc Cellsmentioning

confidence: 99%

PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer

Agarwal

Chakravarthi

Behring

et al. 2020

Cancers

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The identification of colorectal cancer (CRC) molecular targets is needed for the development of drugs that improve patient survival. We investigated the functional role of phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), a de novo purine biosynthetic enzyme involved in DNA synthesis, in CRC progression and metastasis by using cell and animal models. Its clinical utility was assessed in human CRC samples. The expression of PAICS was regulated by miR-128 and transcriptionally activated by Myc in CRC cells. Increased expression of PAICS was involved in proliferation, migration, growth, and invasion of CRC cells irrespective of the p53 and microsatellite status. In mice, the depletion of PAICS in CRC cells led to reduced tumor growth and metastatic cell dissemination to the liver, lungs, and bone. Positron emission tomography imaging showed significantly reduced metastatic lesions in stable PAICS knockdown CRC cells. In cells with PAICS knockdown, there was upregulation of the epithelial mesenchymal transition marker, E-cadherin, and bromodomain inhibitor, JQ1, can target its increased expression by blocking Myc. PAICS was overexpressed in 70% of CRCs, and was associated with poor 5-year survival independent of the pathologic stage, patient’s race, gender, and age. Overall, the findings point to the usefulness of PAICS targeting in the treatment of aggressive colorectal cancer.

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“…В ряде исследований была показана роль ПКСζ в регуляции роста клеток первичной опухоли и реализации механизмов метастазирования при раке молочной железы, толстой кишки, гепатоцеллюлярной карциномы [67][68][69].…”

Section: значение протеинкиназы сζ в онкологииunclassified

The role of lipid metabolism disorders, atypical isoforms of protein kinase C, and mutational status of cytosolic and mitochondrial forms of isocitrate dehydrogenase in carcinogenesis of glial tumors

Никитин¹,

Потапов²,

Ryzhova³

et al. 2018

Vopr. neirokhir.

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The relationship between molecular genetic and metabolic disorders is one of the challenges of modern oncology. In this review, we consider lipid metabolism and its changes as one of the factors of oncogenesis of glial tumors. Also, we demonstrate that the genome and the metabolome are interconnected by a large number of links, and the metabolic pathways, during their reorganization, are able to drastically affect the genetic structure of the cell and, in particular, cause its tumor transformation. Our own observations and analysis of the literature data allow us to conclude that mass spectrometry is a highly accurate current method for assessing metabolic disorders at the cellular level. The use of mass spectrometry during surgery allows the neurosurgeon to obtain real-time data on the level of specific molecular markers in the resected tissue, thereby bringing intraoperative navigation techniques to the molecular level. The generation of molecular fingerprints for each tumor significantly complements the available neuroimaging, molecular genetic, and immunohistochemical data.

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PKCζ Promotes Breast Cancer Invasion by Regulating Expression of E-cadherin and Zonula Occludens-1 (ZO-1) via NFκB-p65

Cited by 32 publications

References 112 publications

Targeting Rho GTPase Signaling Networks in Cancer

Targeting Rho GTPase Signaling Networks in Cancer

PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer

The role of lipid metabolism disorders, atypical isoforms of protein kinase C, and mutational status of cytosolic and mitochondrial forms of isocitrate dehydrogenase in carcinogenesis of glial tumors

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