Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147

Li, Min; Zhai, Qihui; Bharadwaj, Uddalak; Wang, Hao; Li, Fēi; Fisher, William E.; Chen, Changyi; Yao, Qizhi

doi:10.1002/cncr.21862

Cited by 140 publications

(138 citation statements)

References 31 publications

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“…Our studies identified CD147 as an essential component of the cell-surface signaling receptor to CypA and CypB [10;11;13]. This notion has been supported in a number of subsequent publications [14][15][16]. CypA is incorporated into HIV-1 particles during virus morphogenesis through a specific interaction with the CA domain of the Gag precursor polyprotein [17][18][19][20] and plays an essential role in the early steps of the HIV-1 life cycle [21;22].…”

Section: Introductionsupporting

confidence: 69%

CD147 stimulates HIV-1 infection in a signal-independent fashion

Pushkarsky

Yurchenko

Laborico

et al. 2007

Biochemical and Biophysical Research Communications

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CD147 is a type I transmembrane protein previously identified as a signal transducing receptor for extracellular cyclophilins. CD147-expressing cells exhibit a characteristic activation of extracellularsignal regulated kinase 1 and 2 (ERK1/2) in response to stimulation with cyclophilin A (CypA). CD147 was also shown to enhance HIV-1 infection in a CypA-dependent fashion, but the role of signaling in this activity of CD147 has not been investigated. In this report, we demonstrate that neither mutations incapacitating signaling response of CD147 to CypA stimulation, nor inhibitor of ERK activation, reduced susceptibility of cells to HIV-1 infection. Surprisingly, truncation of the cytoplasmic tail of CD147 did not abolish signaling response to CypA, but reduced infection by HIV-1 to the level observed in control cells. These results indicate that CD147 enhances HIV-1 replication in a signaling-independent fashion through specific events mediated by the cytoplasmic domain of the protein.

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Section: Introductionsupporting

confidence: 69%

CD147 stimulates HIV-1 infection in a signal-independent fashion

Pushkarsky

Yurchenko

Laborico

et al. 2007

Biochemical and Biophysical Research Communications

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“…Upregulation of CypA or CypB has been found in primary human cancers. 34,[36][37][38][39][40] In some cases, this upregulation has been associated with enhanced metastasis, radioresistance and poor clinical prognosis. 41,42 Although the direct correlation between expression of cyclophilins and phosphorylation of p38MAPK has not been established, increased levels of phosphorylated p38MAPK have been described in various cancers.…”

Section: Discussionmentioning

confidence: 99%

Proline isomerisation as a novel regulatory mechanism for p38MAPK activation and functions

et al. 2016

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The stress-induced p38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in multiple physiological processes, including cancer. In turn, p38MAPK phosphorylation at Thr180 and Tyr182 is a key regulatory mechanism for its activation and functions. Here we show that this mechanism is actively regulated through isomerisation of Pro224. Different cyclophilins can isomerise this proline residue and modulate the ability of upstream kinases to phosphorylate Thr180 and Tyr182. In vivo mutation of Pro224 to Ile in endogenous p38MAPK significantly reduced its phosphorylation and activity. This resulted in attenuation of p38MAPK signalling, which in turn caused an enhanced apoptosis and sensitivity to a DNA-damaging drug, cisplatin. We further found a reduction in size and number of lesions in homozygous mice carrying the p38MAPK P224I substitution in a K-ras model of lung tumorigenesis. We propose that cyclophilin-dependent isomerisation of p38MAPK is an important novel mechanism in regulating p38MAPK phosphorylation and functions. Thus, inhibition of this process, including with drugs that are in clinical trials, may improve the efficacy of current anti-cancer therapeutic regimes.

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“…α-enolase is a plasminogen-binding protein and also appears to play a major role in the promotion of plasminogen activation by leukocytic cells [74]. Peptidylprolyl isomerase (cyclophilin A) has been associated with a number of cancer histiotypes including breast [75] and pancrease [76,77], and has been implicated in cellular resistance to hypoxia-and Cisplatininduced cell death [78] and resistance to aplidin [79]. Its secretion from regressive tumor masses has been previously been studied by MS [80] and it has been profiled as one of a number of glycolytic enzymes increased in pancreatic cancerous tissues [76].…”

Section: Non-classical Secretionmentioning

confidence: 99%

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

et al. 2007

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Proteins secreted (the secretome) from cancer cells are potentially useful as biomarkers of the disease. Using LC-MS/MS, the secreted proteomes from a series of isogenic breast cancer cell lines varying in aggressiveness were analyzed by mass spectrometry: non-tumorigenic MCF10A, premalignant/ tumorigenic MCF10AT, tumorigenic/locally invasive MCF10 DCIS.com and tumorigenic/ metastatic MCF 10CA cl. D. Proteomes were obtained from conditioned serum-free media, partially fractionated using a small reverse phase C2 column and digested with trypsin for analysis by LC-MS/MS, using a method previously shown to give highly enriched secreted proteomes (Mbeunkui, et. al., J. Prot. Res. 5, 899-906 2006). The search files produced from 5 analyses (3 separate preparations) were combined for database searching (Mascot) which produced a list of over 250 proteins from each cell line. The aim was to discover highly secreted proteins which changed significantly in abundance corresponding with aggressiveness. The most apparent changes were observed for alpha-1-antichymotrypsin and galectin-3-binding protein which were highly secreted proteins from MCF10 DCIS.com and MCF10CA cl. D, yet undetected in the MCF10A and MCF10AT cell lines. Other proteins showing increasing abundance in the more aggressive cell lines included alpha-1-antitrypsin, cathepsin D and lysyl oxidase. The S100 proteins, often associated with metastasis, showed variable changes in abundance. While the cytosolic proteins were low (e.g. actin and tubulin), there was significant secretion of proteins often associated with the cytoplasm. These proteins were all predicted as products of non-classical secretion (SecretomeIP, Center for Biological Sequence Analysis). The LC-MS/MS results were verified for five selected proteins by western blot analysis, and the relevance of other significant proteins is discussed. Comparisons with two other aggressive breast cancer cell lines are included and the protein with consistent association with aggressiveness in all lines, and in unrelated cancer cells, was the galectin-3-binding protein which has been associated with breast, prostate and colon cancer earlier, supporting the approach and findings. This analysis of an isogenic series of cell lines suggests the potential usefulness of the secretome for identifying prospective markers for the early detection and aggressiveness/progression of cancer.

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Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147

Cited by 140 publications

References 31 publications

CD147 stimulates HIV-1 infection in a signal-independent fashion

CD147 stimulates HIV-1 infection in a signal-independent fashion

Proline isomerisation as a novel regulatory mechanism for p38MAPK activation and functions

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

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