FKBP4 Accelerates Malignant Progression of Non-Small-Cell Lung Cancer by Activating the Akt/mTOR Signaling Pathway

Meng, Wen; Meng, Jingfei; Jiang, Hong; Feng, Xing; Wei, Dong; Ding, Qingsong

doi:10.1155/2020/6021602

Cited by 16 publications

(16 citation statements)

References 23 publications

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“…For AKT signalling (Fig. 5 ), we found the decreased expressions of NCSTN [ 43 ], TPD52L2 [ 44 ], PSMC2 [ 45 ], FKBP4 [ 46 ] and ARHGAP1 [ 47 ] which activate AKT signalling (Fig. 4 ).…”

Section: Resultsmentioning

confidence: 99%

Proteomics-based investigation of cerebrovascular molecular mechanisms in cerebral amyloid angiopathy by the FFPE-LMD-PCT-SWATH method

Handa

Sasaki

Takao

et al. 2022

Fluids Barriers CNS

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Background Cerebral amyloid angiopathy (CAA) occurs in 80% of patients with Alzheimer’s disease (AD) and is mainly caused by the abnormal deposition of Aβ in the walls of cerebral blood vessels. Cerebrovascular molecular mechanisms in CAA were investigated by using comprehensive and accurate quantitative proteomics. Methods Concerning the molecular mechanisms specific to CAA, formalin-fixed paraffin-embedded (FFPE) sections were prepared from patients having AD neuropathologic change (ADNC) with severe cortical Aβ vascular deposition (ADNC +/CAA +), and from patients having ADNC without vascular deposition of Aβ (ADNC +/CAA −; so called, AD). Cerebral cortical vessels were isolated from FFPE sections using laser microdissection (LMD), processed by pressure cycling technology (PCT), and applied to SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Results The protein expression levels of 17 proteins in ADNC +/CAA +/H donors (ADNC +/CAA + donors with highly abundant Aβ in capillaries) were significantly different from those in ADNC +/CAA − and ADNC −/CAA − donors. Furthermore, we identified 56 proteins showing more than a 1.5-fold difference in average expression levels between ADNC +/CAA + and ADNC −/CAA − donors, and were significantly correlated with the levels of Aβ or Collagen alpha-2(VI) chain (COL6A2) (CAA markers) in 11 donors (6 ADNC +/CAA + and 5 ADNC −/CAA −). Over 70% of the 56 proteins showed ADNC +/CAA + specific changes in protein expression. The comparative analysis with brain parenchyma showed that more than 90% of the 56 proteins were vascular-specific pathological changes. A literature-based pathway analysis showed that 42 proteins are associated with fibrosis, oxidative stress and apoptosis. This included the increased expression of Heat shock protein HSP 90-alpha, CD44 antigen and Carbonic anhydrase 1 which are inhibited by potential drugs against CAA. Conclusions The combination of LMD-based isolation of vessels from FFPE sections, PCT-assisted sample processing and SWATH analysis (FFPE-LMD-PCT-SWATH method) revealed for the first time the changes in the expression of many proteins that are involved in fibrosis, ROS production and cell death in ADNC +/CAA + (CAA patients) vessels. The findings reported herein would be useful for developing a better understanding of the pathology of CAA and for promoting the discovery and development of drugs and biomarkers for CAA.

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“…For AKT signalling (Fig. 5 ), we found the decreased expressions of NCSTN [ 43 ], TPD52L2 [ 44 ], PSMC2 [ 45 ], FKBP4 [ 46 ] and ARHGAP1 [ 47 ] which activate AKT signalling (Fig. 4 ).…”

Section: Resultsmentioning

confidence: 99%

Proteomics-based investigation of cerebrovascular molecular mechanisms in cerebral amyloid angiopathy by the FFPE-LMD-PCT-SWATH method

Handa

Sasaki

Takao

et al. 2022

Fluids Barriers CNS

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“…Accordantly, loss of FKBP4 did not trigger apoptosis of COAD cells either (Fig S4C). Because the high FKBP4 level is known to promote migration and invasion of lung cancer cell (Meng et al, 2020;Zong et al, 2021), we thus wondered whether it plays a similar role in COAD cells. However, we did not observe a significant change in the migration/invasion level upon FKBP4 depletion in COAD cells (Fig S4D and E), suggesting that FKBP4 does not play a role in controlling COAD cell migration and invasion.…”

Section: Loss Of Ims-localized Fkbp4 Confers Enhanced Sensitivity Of ...mentioning

confidence: 99%

FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration

et al. 2022

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Mitochondrial respiration and metabolism play a key role in the pathogenesis and progression of colon adenocarcinoma (COAD). Here, we report a functional pool of FKBP4, a co-chaperone protein, in the mitochondrial intermembrane space (IMS) of colon cancer cells. We found that IMS-localized FKBP4 is essential for the maintenance of mitochondrial respiration, thus contributing to the sensitivity of COAD cells to 5-fluorouracil (5-FU). Mechanistically, FKBP4 interacts with COA6 and controls the assembly of the mitochondrial COA6/SCO1/SCO2 complex, thereby governing COA6-regulated biogenesis and activity of mitochondrial cytochrome c oxidase (complex IV). Thus, our data reveal IMS-localized FKBP4 as a novel regulator of 5-FU sensitivity in COAD, linking mitochondrial respiration to 5-FU sensitivity in COAD.

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“…This state had significant overexpression of genes involved in cancer metastasis and associated with poor prognosis. The differentially expressed genes included ANXA1, FKBP4, LCN2, VNN1, TCN1, TACSTD2 (encoding TROP2), DUOXA2, CAECAM5, CAECAM6 and members of the Kallikrein family genes (KLK6, KLK8, KLK10 and KLK11) [36][37][38][39][40][41][42][43][44][45][46][47] (Fig. 3D, Supplemental Table 4).…”

Section: Genes Defining Each Cell Statementioning

confidence: 99%

Distinct cell states define the developmental trajectories of mucinous appendiceal neoplasms towards pseudomyxoma metastases

Ayala

Sathe

Bai

et al. 2022

Preprint

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Objective: Appendiceal mucinous neoplasms (AMN) start in the appendix. Following appendiceal perforation, these tumor metastasize, leading to pseudomyxoma peritonei (PMP). We characterized the distinct cell types and states of AMN and PMP. Design: Single-cell RNA-seq was conducted on 31 samples including AMNs, PMP metastases and a subset of matched normal appendix or omental tissues. We validated the findings with immunohistochemistry, mass spectrometry on malignant ascites from PMP patients and gene expression data from an independent set of 63 PMPs. Results: AMNs and PMPs had epithelial tumor cells with goblet features including the elevated expression of mucin genes. Among these tumors, we identified developmental cell states of the epithelium that ranged from progenitor phase to goblet cell differentiation. Metastatic PMP cells had a distinct cell state with gene expression signatures indicative of mTOR and RAS signaling pathways. A series of cancer genes defined this metastatic cell state. Matched PMP metastases from the same patient differed in their expression signatures. The cell state signatures were validated in external datasets containing 63 PMP patients. AMN and PMP tumor microenvironment (TME) contained CD4 T follicular helper-like cells and cytotoxic CD8 T cells. Conclusion: AMN and PMP tumors consisted of progenitor epithelial cells that differentiate into goblet cells. PMP cells had a distinct cell state indicative of metastasis. The TME was infiltrated with T cells, suggesting that immunotherapy is a potential treatment.

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FKBP4 Accelerates Malignant Progression of Non-Small-Cell Lung Cancer by Activating the Akt/mTOR Signaling Pathway

Cited by 16 publications

References 23 publications

Proteomics-based investigation of cerebrovascular molecular mechanisms in cerebral amyloid angiopathy by the FFPE-LMD-PCT-SWATH method

Proteomics-based investigation of cerebrovascular molecular mechanisms in cerebral amyloid angiopathy by the FFPE-LMD-PCT-SWATH method

FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration

Distinct cell states define the developmental trajectories of mucinous appendiceal neoplasms towards pseudomyxoma metastases

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