PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle

Yanagi, Teruki; Hata, Hiroo; Mizuno, Eri; Kitamura, Shinya; Imafuku, Kimiaki; Nakazato, Shinichi; Wang, Lei; Nishihara, Hiroshi; Tanaka, Shinya; Shimizu, Hiroshi

doi:10.1016/j.jdermsci.2017.02.281

Cited by 25 publications

(32 citation statements)

References 39 publications

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“…For CDK16 several studies described a significant upregulation of this kinase in different tumor entities compared to adjacent normal tissue. The elevated expression of CDK16 correlates positively with the tumor aggressiveness and is required for tumor cell proliferation [57][58][59][60][61] . In light of these recent findings, our data suggest that CDK16 promotes tumor growth by enhancing tumor-supportive autophagy 62 .…”

Section: Articlementioning

confidence: 99%

AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy

et al. 2020

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The AMP-activated protein kinase (AMPK) is a master sensor of the cellular energy status that is crucial for the adaptive response to limited energy availability. AMPK is implicated in the regulation of many cellular processes, including autophagy. However, the precise mechanisms by which AMPK controls these processes and the identities of relevant substrates are not fully understood. Using protein microarrays, we identify Cyclin Y as an AMPK substrate that is phosphorylated at Serine 326 (S326) both in vitro and in cells. Phosphorylation of Cyclin Y at S326 promotes its interaction with the Cyclin-dependent kinase 16 (CDK16), thereby stimulating its catalytic activity. When expressed in cells, Cyclin Y/CDK16 is sufficient to promote autophagy. Moreover, Cyclin Y/CDK16 is necessary for efficient AMPK-dependent activation of autophagy. This functional interaction is mediated by AMPK phosphorylating S326 of Cyclin Y. Collectively, we define Cyclin Y/CDK16 as downstream effector of AMPK for inducing autophagy.

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Section: Articlementioning

confidence: 99%

AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy

et al. 2020

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“…Dewaxed tissue sections (4.0-5.0 mm) were immunostained as reported previously using primary antibodies (22). The application of the primary antibody was followed by incubation with goat anti-mouse or rabbit polymer-based EnVision-HRPenzyme conjugate (Dako, Japan).…”

Section: Ihcmentioning

confidence: 99%

Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma

et al. 2018

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TRIM29 (tripartite motif-containing protein 29) is a TRIM family protein that has been implicated in breast, colorectal, and pancreatic cancers. However, its role in stratified squamous epithelial cells and tumors has not been elucidated.Here, we investigate the expression of TRIM29 in cutaneous head and neck squamous cell carcinomas (SCC) and its functions in the tumorigenesis of such cancers. TRIM29 expression was lower in malignant SCC lesions than in adjacent normal epithelial tissue or benign tumors. Lower expression of TRIM29 was associated with higher SCC invasiveness. Primary tumors of cutaneous SCC showed aberrant hypermethylation of TRIM29. Depletion of TRIM29 increased cancer cell migration and invasion; conversely, overexpression of TRIM29 suppressed these. Comprehensive proteomics and immuno-precipitation analyses identified keratins and keratin-interacting protein FAM83H as TRIM29 interactors. Knockdown of TRIM29 led to ectopic keratin localization of keratinocytes. In primary tumors, lower TRIM29 expression correlated with the altered expression of keratins. Our findings reveal an unexpected role for TRIM29 in regulating the distribution of keratins, as well as in the migration and invasion of SCC. They also suggest that the TRIM29-keratin axis could serve as a diagnostic and prognostic marker in stratified epithelial tumors and may provide a target for SCC therapeutics.Significance: These findings identify TRIM29 as a novel diagnostic and prognostic marker in stratified epithelial tissues. Cancer Res; 78(24); 6795-806. Ó2018 AACR.

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“…To investigate the role of Cdk16 in cancerous cells, we performed gene-knockdown experiments targeting Cdk16 ( 44 – 47 ). In cell lines of cutaneous SCC, prostate cancer, breast cancer, cervical cancer, and melanoma, knockdown of Cdk16 inhibited cancer cell proliferation, and induced apoptosis over time.…”

Section: Recent Progress In Cutaneous Scc Therapeuticsmentioning

confidence: 99%

“…The knockdown of Cdk16 modulated p27 (Ser10) phosphorylation, leading to p27 accumulation in cancerous cells. In tumor xenografts of cutaneous SCC cells, the inducible conditional knockdown of Cdk16 suppressed tumor growth ( 47 ).…”

Section: Recent Progress In Cutaneous Scc Therapeuticsmentioning

confidence: 99%

Novel Therapeutic Targets in Cutaneous Squamous Cell Carcinoma

2018

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Cutaneous squamous cell carcinoma (SCC) is one of the common cancers in Caucasians, accounting for 20–30% of cutaneous malignancies. The risk of metastasis is low in most patients; however, aggressive SCC is associated with very high mortality and morbidity. Although cutaneous SCC can be treated with surgical removal, radiation and chemotherapy singly or in combination, the prognosis of patients with metastatic SCC is poor. Recently, the usage of immune checkpoint blockades has come under consideration. To develop effective therapies that are less toxic than existing ones, it is crucial to achieve a detailed characterization of the molecular mechanisms that are involved in cutaneous SCC pathogenesis and to identify new drug targets. Recent studies have identified novel molecules that are associated with SCC carcinogenesis and progression. This review focuses on recent advances in molecular studies involving SCC tumor development, as well as in new therapeutics that have become available to clinicians.

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PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle

Cited by 25 publications

References 39 publications

AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy

AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy

Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma

Novel Therapeutic Targets in Cutaneous Squamous Cell Carcinoma

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