Repression of cancer cell senescence by PKCι

Paget, Judith A; Restall, Ian J.; Daneshmand, Manijeh; Mersereau, J A; Simard, Manon A.; Parolin, Doris A. E.; Lavictoire, Sylvie J.; Amin, Moein; Islam, Shahidul; Lorimer, Ian A. J.

doi:10.1038/onc.2011.524

Cited by 26 publications

(33 citation statements)

References 49 publications

(64 reference statements)

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“…Thus, PKCl/iIS110 could be of tremendous clinical significance and might serve as a platform to identify specific biomarkers, which could predict invasive progression of breast cancer. Altogether, these observations and previous reports 28,29 indicate significance of PKCl/i signaling during the breast cancer disease progression including growth, invasion, relapse/metastasis and survival.…”

Section: Discussionsupporting

confidence: 53%

“…Immunohistochemical analysis of PKCl/i expression indicated significant increase in ER-and HER2-positive IDC samples compared with normal breast and DCIS ( Figure 1a, Supplementary Figures S1c and d) and supported previous reports. 28,29 Importantly, we also observed significant higher expression of PKCl/i in TNBC subtypes compared with normal breast and DCIS (Figures 1a-c, Supplementary Figures S1c and d). In all IDC samples, the induced PKCl/i localization was detected in both cytoplasm and nuclei, (Figure 1d and Supplementary Figure S1b) with a few cases showing focal (5-25%) nuclear staining.…”

Section: Resultsmentioning

confidence: 54%

“…28 Next, we collected multiple human metastatic breast cancer samples (n ¼ 10) from distal organs such as the bone, brain, chest wall, colon, gallbladder, liver, lung and ovary to test PKCl/i expression and phosphorylation ( Figure 1e). We found that similar to IDC and lymph node metastasis, 29 PKCl/i is highly expressed and phosphorylated in the metastatic breast cancers with predominant nuclear localization of phosphoPKCl/i (Figure 1e). Collectively, these results and previous reports 28,29 strongly correlate higher expression and activation of PKCl/i with invasive progression of breast cancer including TNBC subtypes to develop local and distal metastasis.…”

Section: Resultsmentioning

confidence: 87%

“…We found that similar to IDC and lymph node metastasis, 29 PKCl/i is highly expressed and phosphorylated in the metastatic breast cancers with predominant nuclear localization of phosphoPKCl/i (Figure 1e). Collectively, these results and previous reports 28,29 strongly correlate higher expression and activation of PKCl/i with invasive progression of breast cancer including TNBC subtypes to develop local and distal metastasis.…”

Section: Resultsmentioning

confidence: 87%

“…27 Recently, few studies have been reported higher expression of PKCl/i in ER/PRand HER-positive breast cancer and also in lymph node metastases. 28, 29 Kojima et. al.…”

mentioning

confidence: 99%

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PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis

et al. 2014

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Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), and the patients with TNBC are often diagnosed with higher rates of recurrence and metastasis. Because of the absence of ER, PR and HER2/neu expressions, TNBC patients are insensitive to HER2-directed and endocrine therapies available for breast cancer treatment. Here, we report that expression of atypical protein kinase C isoform, PKCk/i, significantly increased and activated in all invasive breast cancer (invasive ductal carcinoma or IDC) subtypes including the TNBC subtype. Because of the lack of targeted therapies for TNBC, we choose to study PKCk/i signaling as a potential therapeutic target for TNBC. Our observations indicated that PKCk/i signaling is highly active during breast cancer invasive progression, and metastatic breast cancers, the advanced stages of breast cancer disease that developed more frequently in TNBC patients, are also characterized with high levels of PKCk/i expression and activation. Functional analysis in experimental mouse models revealed that depletion of PKCk/i significantly reduces TNBC growth as well as lung metastatic colonization. Furthermore, we have identified a PKCk/i-regulated gene signature consisting of 110 genes, which are significantly associated with indolent to invasive progression of human breast cancer and poor prognosis. Mechanistically, cytokines such as TGFb and IL1b could activate PKCk/i signaling in TNBC cells and depletion of PKCk/i impairs NF-jB p65 (RelA) nuclear localization. We observed that cytokine-PKCk/i-RelA signaling axis, at least in part, involved in modulating gene expression to regulate invasion of TNBC cells. Overall, our results indicate that induction and activation of PKCk/i promote TNBC growth, invasion and metastasis. Thus, targeting PKCk/i signaling could be a therapeutic option for breast cancer, including the TNBC subtype.

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Section: Discussionsupporting

confidence: 53%

Section: Resultsmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 87%

“…27 Recently, few studies have been reported higher expression of PKCl/i in ER/PRand HER-positive breast cancer and also in lymph node metastases. 28, 29 Kojima et. al.…”

mentioning

confidence: 99%

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PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis

et al. 2014

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Immortality of cell lines: challenges and advantages of establishment

Irfan-Maqsood

Matin

Bahrami

et al. 2013

Cell Biology International

130

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Cellular immortality happens upon impairment of cell-cycle checkpoint pathways (p53/p16/pRb), reactivation or up-regulation of telomerase enzyme, or upregulation of some oncogenes or oncoproteins leading to a higher rate of cell division.There are also some other factors and mechanisms involved in immortalisation, which need to be discovered. Immortalisation of cells derived from different sources and establishment of immortal cell lines has proven useful in understanding the molecular pathways governing cell developmental cascades in eukaryotic, especially human, cells. After the breakthrough of achieving the immortal cells and understanding their critical importance in the field of molecular biology, intense efforts have been dedicated to establish cell lines useful for elucidating the functions of telomerase, developmental lineage of progenitors, self-renewal potency, cellular transformation, differentiation patterns and some bioprocesses, like odontogenesis. Meanwhile, discovering the exact mechanisms of immortality, a major challenge for science yet, is believed to open new gateways toward understanding and treatment of cancer in the long term. This review summarises the methods involved in establishing immortality, its advantages and the challenges still being faced in this field.

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Par Proteins in Tumor Formation and Progression

Mescher

Iden

2015

Cell Polarity 2

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Repression of cancer cell senescence by PKCι

Cited by 26 publications

References 49 publications

PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis

PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis

Immortality of cell lines: challenges and advantages of establishment

Par Proteins in Tumor Formation and Progression

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