Protein Kinase-ζ Inhibits Collagen I–Dependent and Anchorage-Independent Growth and Enhances Apoptosis of Human Caco-2 Cells

Mustafi, Reba; Cerda, Sonia R.; Chumsangsri, Anusara; Fichera, Alessandro; Bissonnette, Marc

doi:10.1158/1541-7786.mcr-06-0057

Cited by 32 publications

(34 citation statements)

References 55 publications

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“…PKCζ also stimulates motility and maturation of human CD34+ hematopoietic stem and progenitor cells (37). Forced expression of PKCζ also causes decreased anchorage-independent transformed growth, increased differentiation and enhanced apoptosis in CaCo2 human colon cancer cells (38). Interestingly, PKCζ expression is decreased in azoxymethane (AOM)-induced colon tumors in rats, and expression of a dominant negative, kinase-deficient PKCζ (kdPKCζ) mutant inhibits soft agar growth of CaCo2 cells (38), suggesting that loss of PKCζ expression may promote transformed growth and colon tumor formation.…”

Section: Atypical Pkcs In Human Cancermentioning

confidence: 99%

Protein kinase Cι: Human oncogene, prognostic marker and therapeutic target

Fields

Regala

2007

Pharmacological Research

112

113

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The Protein kinase C (PKC) family of serine/threonine kinases has been the subject of intensive study in the field of cancer since their initial discovery as major cellular receptors for the tumor promoting phorbol esters nearly thirty years ago. However, despite these efforts, the search for a direct genetic link between members of the PKC family and human cancer has yielded only circumstantial evidence that any PKC isozyme is a true cancer gene. This situation changed in the past year with the discovery that atypical protein kinase C iota (PKCι) is a bonafide human oncogene. PKCι is required for the transformed growth of human cancer cells and the PKCι gene is the target of tumor-specific gene amplification in multiple forms of human cancer. PKCι participates in multiple aspects of the transformed phenotype of human cancer cells including transformed growth, invasion and survival. Herein, we review pertinent aspects of atypical PKC structure, function and regulation that relate to the role of these enzymes in oncogenesis. We discuss the evidence that PKCι is a human oncogene, review mechanisms controlling PKCι expression in human cancers, and describe the molecular details of PKCι-mediated oncogenic signaling. We conclude with a discussion of how oncogenic PKCι signaling has been successfully targeted to identify a novel, mechanism-based therapeutic drug currently entering clinical trials for treatment of human lung cancer. Throughout, we identify key unanswered questions and exciting future avenues of investigation regarding this important oncogenic molecule.

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Section: Atypical Pkcs In Human Cancermentioning

confidence: 99%

Protein kinase Cι: Human oncogene, prognostic marker and therapeutic target

Fields

Regala

2007

Pharmacological Research

112

113

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“…For example, PKCζ inhibits growth and promotes differentiation and apoptosis in colon cancer cells. The inhibitory effect of PKCζ on the transformed phenotype of these cells suggests that down-regulation of PKCζ may contribute to colon tumorigenesis [215]. PKCζ also exhibits a pro-apoptotic function in ovarian cancer [216].…”

Section: Atypical Pkcs ζ and ι: Opposite Roles In Cancermentioning

confidence: 99%

Protein kinase C and cancer: what we know and what we do not

et al. 2013

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Since their discovery in the late 1970’s, protein kinase C (PKC) isozymes represent one of the most extensively studied signaling kinases. PKCs signal through multiple pathways and control the expression of genes relevant for cell cycle progression, tumorigenesis and metastatic dissemination. Despite the vast amount of information concerning the mechanisms that control PKC activation and function in cellular models, the relevance of individual PKC isozymes in the progression of human cancer is still a matter of controversy. Although the expression of PKC isozymes is altered in multiple cancer types, the causal relationship between such changes and the initiation and progression of the disease remains poorly defined. Animal models developed in the last years helped to better understand the involvement of individual PKCs in various cancer types and in the context of specific oncogenic alterations. Unraveling the enormous complexity in the mechanisms by which PKC isozymes impact on tumorigenesis and metastasis is key for reassessing their potential as pharmacological targets for cancer treatment.

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“…Like PKC , PKC protein expression does not differ between normal and cancerous tissues, but PKC does appear to be associated with the inhibition of colon cancer cell growth and enhancement of differentiation and apoptosis [136,137]. In a recent study, the loss of PKC resulted in an increase in intestinal carcinogenesis, upregulation of two metabolic enzymes, 3-phosphoglycerate dehydrogenase and phosphoserine aminotransferase-1, and inhibition of caspase-3 activation.…”

Section: Colonmentioning

confidence: 99%

Protein Kinase C (PKC) Isozymes and Cancer

Kang

2014

New Journal of Science

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Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine kinases, which can be further classified into three PKC isozymes subfamilies: conventional or classic, novel or nonclassic, and atypical. PKC isozymes are known to be involved in cell proliferation, survival, invasion, migration, apoptosis, angiogenesis, and drug resistance. Because of their key roles in cell signaling, PKC isozymes also have the potential to be promising therapeutic targets for several diseases, such as cardiovascular diseases, immune and inflammatory diseases, neurological diseases, metabolic disorders, and multiple types of cancer. This review primarily focuses on the activation, mechanism, and function of PKC isozymes during cancer development and progression.

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Protein Kinase-ζ Inhibits Collagen I–Dependent and Anchorage-Independent Growth and Enhances Apoptosis of Human Caco-2 Cells

Cited by 32 publications

References 55 publications

Protein kinase Cι: Human oncogene, prognostic marker and therapeutic target

Protein kinase Cι: Human oncogene, prognostic marker and therapeutic target

Protein kinase C and cancer: what we know and what we do not

Protein Kinase C (PKC) Isozymes and Cancer

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