Dysregulation and crosstalk of cellular signaling pathways in colon carcinogenesis

Wu, William Ka Kei; Wang, Xiaoju; Cheng, Alfred S.L.; Luo, Millore X.M.; Ng, Simon Siu Man; To, Ka Fai; Chan, Francis K.L.; Cho, Chi H.; Sung, Joseph J.Y.; Yu, Jun

doi:10.1016/j.critrevonc.2012.11.009

Cited by 88 publications

(95 citation statements)

References 299 publications

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“…Increase in PNN on the other hand further cooperates with KRT1/KRT9/DSP to promote desmosomal tethering. Changes in Wnt and TGFb networks after STMN1 KD (FZD7, TGFB2, TGFB3 and SMAD2, SMAD4) also suggest plausible suppression of experimental metastasis (3) through a complex myriad of signaling modulation (10). Indeed, loss of SERPINE1 expression was a downstream effect of abrogated TGFb signal relay, with low expression of SMADs (11).…”

Section: Stmn1 Silencing Reverses Metastatic and Emt Transcriptional mentioning

confidence: 99%

Unbiased Proteomic and Transcript Analyses Reveal that Stathmin-1 Silencing Inhibits Colorectal Cancer Metastasis and Sensitizes to 5-Fluorouracil Treatment

Tan

et al. 2014

Molecular Cancer Research

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Colorectal cancer metastasis is a major cause of mortality worldwide, which may only be controlled with novel methods limiting tumor dissemination and chemoresistance. High stathmin-1 (STMN1) expression was previously established as a hallmark of colorectal cancer progression and predictor of poor survival; however, the mechanism of action is less clear. This work demonstrates that STMN1 silencing arrests tumor-disseminative cascades by inhibiting multiple metastatic drivers, and repressing oncogenic and mesenchymal transcription. Using a sensitive iTRAQ labeling proteomic approach that quantified differential abundance of 4562 proteins, targeting STMN1 expression was shown to reinstate the default cellular program of metastatic inhibition, and promote cellular adhesion via amplification of hemidesmosomal junctions and intermediate filament tethering. Silencing STMN1 also significantly improved chemoresponse to the classical colorectal cancer therapeutic agent, 5FU, via a novel caspase-6 (CASP6)-dependent mechanism. Interestingly, the prometastatic function of STMN1 was independent of p53 but required phosphorylations at S25 or S38; abrogating phosphorylative events may constitute an alternative route to achieving metastatic inhibition. These findings establish STMN1 as a potential target in antimetastatic therapy, and demonstrate the power of an approach coupling proteomics and transcript analyses in the global assessment of treatment benefits and potential side-effects.Implications: Stathmin-1 is a potential candidate in colorectal cancer therapy that targets simultaneously the twin problems of metastatic spread and chemoresistance.

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Section: Stmn1 Silencing Reverses Metastatic and Emt Transcriptional mentioning

confidence: 99%

Unbiased Proteomic and Transcript Analyses Reveal that Stathmin-1 Silencing Inhibits Colorectal Cancer Metastasis and Sensitizes to 5-Fluorouracil Treatment

Tan

et al. 2014

Molecular Cancer Research

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“…Dysregulation of Notch receptors, ligands, or target genes is noted in various cancer cells (1,2). Notch signaling inhibition has been demonstrated to attenuate cancer cell proliferation/cell cycle progression, to decrease cancer cell viability, and to increase cell apoptosis in various types of cancer (1,(3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Expression and influence of Notch signaling in oral squamous cell carcinoma

2016

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“…Many of these downstream pathways are also dysregulated in cancer (Wu et al, 2013). Understanding the nature of interactions between Ras and other major cellular signalling pathways is therefore essential for development of effective strategies for suppression of Ras-driven cancer (Wu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Oncogenic K-Ras suppresses IP3-dependent Ca2+ release through remodeling of IP3Rs isoform composition and ER luminal Ca2+ levels in colorectal cancer cell lines

Pierro

Cook

Foets

et al. 2014

Journal of Cell Science

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Dysregulation and crosstalk of cellular signaling pathways in colon carcinogenesis

Cited by 88 publications

References 299 publications

Unbiased Proteomic and Transcript Analyses Reveal that Stathmin-1 Silencing Inhibits Colorectal Cancer Metastasis and Sensitizes to 5-Fluorouracil Treatment

Unbiased Proteomic and Transcript Analyses Reveal that Stathmin-1 Silencing Inhibits Colorectal Cancer Metastasis and Sensitizes to 5-Fluorouracil Treatment

Expression and influence of Notch signaling in oral squamous cell carcinoma

Oncogenic K-Ras suppresses IP3-dependent Ca2+ release through remodeling of IP3Rs isoform composition and ER luminal Ca2+ levels in colorectal cancer cell lines

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