Abnormal Expression of PFDN4 in Colorectal Cancer: A Novel Marker for Prognosis

Miyoshi, Norikatsu; Ishii, Hideshi; Mimori, Koshi; Nishida, Naohiro; Tokuoka, Masayoshi; Akita, Hirofumi; Sekimoto, Mitsugu; Doki, Yuichiro; Mori, Masaki

doi:10.1245/s10434-010-1138-5

Cited by 27 publications

(34 citation statements)

References 23 publications

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“…In vitro experiments have shown that PFDN4 plays an important role in tumor cell growth, invasiveness, and metastasis [44,45]. However, the role of PFDN4 in cancer progression is unclear because colorectal cancer patients with high tumor PFDN4 expression have been reported to have a better prognosis [45], whereas in the present study HCC patients with gain of 20q13.12-13.33 where PFDN4 located had a worse prognosis and high PFDN4 expression was associated with tumor vascular invasion. The genes ZNF64 and DDX27 have been found upregulated as a consequence of 20q gain in cervical cancer [46], but their functions in cancer development are not well understood.…”

Section: Discussionmentioning

confidence: 47%

“…PFDN4, a transcriptional factor that regulates cell cycle, is highly expressed in breast cancer cell lines and tumor tissues and has been reported as a candidate tumor-related gene [42,43]. In vitro experiments have shown that PFDN4 plays an important role in tumor cell growth, invasiveness, and metastasis [44,45]. However, the role of PFDN4 in cancer progression is unclear because colorectal cancer patients with high tumor PFDN4 expression have been reported to have a better prognosis [45], whereas in the present study HCC patients with gain of 20q13.12-13.33 where PFDN4 located had a worse prognosis and high PFDN4 expression was associated with tumor vascular invasion.…”

Section: Discussionmentioning

confidence: 99%

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Multiple genes identified as targets for 20q13.12–13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma

et al. 2015

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Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Multiple genes identified as targets for 20q13.12–13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma

et al. 2015

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“…Several studies report that chaperones are found at increased levels in many solid tumours and haematological malignancies [5], [6]. Their expression may in part account for the ability of malignant cells to maintain protein homeostasis in the unfavourable hypoxic and acidic microenvironment of the tumour.…”

Section: Introductionmentioning

confidence: 99%

The Cytosolic Chaperonin CCT/TRiC and Cancer Cell Proliferation

2013

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The molecular chaperone CCT/TRiC plays a central role in maintaining cellular proteostasis as it mediates the folding of the major cytoskeletal proteins tubulins and actins. CCT/TRiC is also involved in the oncoprotein cyclin E, the Von Hippel-Lindau tumour suppressor protein, cyclin B and p21ras folding which strongly suggests that it is involved in cell proliferation and tumor genesis. To assess the involvement of CCT/TRiC in tumor genesis, we quantified its expression levels and activity in 18 cancer, one non-cancer human cell lines and a non-cancer human liver. We show that the expression levels of CCT/TRiC in cancer cell lines are higher than that in normal cells. However, CCT/TRiC activity does not always correlate with its expression levels. We therefore documented the expression levels of CCT/TRiC modulators and partners PhLP3, Hop/P60, prefoldin and Hsc/Hsp70. Our analysis reveals a functional interplay between molecular chaperones that might account for a precise modulation of CCT/TRiC activity in cell proliferation through changes in the cellular levels of prefoldin and/or Hsc/p70 and CCT/TRiC client protein availability. Our observation and approaches bring novel insights in the role of CCT/TRiC-mediated protein folding machinery in cancer cell development.

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“…Recent studies have shown that the prefoldin subunit may function independently. PFD4 expression is a prognostic factor in breast and colorectal tumor and cancer cells [22]. PFD2 was identified as a biomarker of bladder cancer cells [23].…”

Section: Discussionmentioning

confidence: 99%

Expression, Functional Characterization, and Preliminary Crystallization of the Cochaperone Prefoldin from the Thermophilic Fungus Chaetomium thermophilum

Morita

Yamamoto

Hori

et al. 2018

IJMS

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Prefoldin is a hexameric molecular chaperone found in the cytosol of archaea and eukaryotes. Its hexameric complex is built from two related classes of subunits, and has the appearance of a jellyfish: Its body consists of a double β-barrel assembly with six long tentacle-like coiled coils protruding from it. Using the tentacles, prefoldin captures an unfolded protein substrate and transfers it to a group II chaperonin. Based on structural information from archaeal prefoldins, mechanisms of substrate recognition and prefoldin-chaperonin cooperation have been investigated. In contrast, the structure and mechanisms of eukaryotic prefoldins remain unknown. In this study, we succeeded in obtaining recombinant prefoldin from a thermophilic fungus, Chaetomium thermophilum (CtPFD). The recombinant CtPFD could not protect citrate synthase from thermal aggregation. However, CtPFD formed a complex with actin from chicken muscle and tubulin from porcine brain, suggesting substrate specificity. We succeeded in observing the complex formation of CtPFD and the group II chaperonin of C. thermophilum (CtCCT) by atomic force microscopy and electron microscopy. These interaction kinetics were analyzed by surface plasmon resonance using Biacore. Finally, we have shown the transfer of actin from CtPFD to CtCCT. The study of the folding pathway formed by CtPFD and CtCCT should provide important information on mechanisms of the eukaryotic prefoldin–chaperonin system.

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Abnormal Expression of PFDN4 in Colorectal Cancer: A Novel Marker for Prognosis

Abstract: The data strongly suggest that PFDN4 expression is a prognostic factor in CRC.

Cited by 27 publications

References 23 publications

Multiple genes identified as targets for 20q13.12–13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma

Multiple genes identified as targets for 20q13.12–13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma

The Cytosolic Chaperonin CCT/TRiC and Cancer Cell Proliferation

Expression, Functional Characterization, and Preliminary Crystallization of the Cochaperone Prefoldin from the Thermophilic Fungus Chaetomium thermophilum

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