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Showing posts with the label colon cancer

Note; The E3 ligase RNF43 inhibits Wnt signaling downstream of mutated beta-catenin by sequestering TCF4 to the nuclear membrane

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The E3 ligase RNF43 inhibits Wnt signaling downstream of mutated beta-catenin by sequestering TCF4 to the nuclear membrane (doi: 10.1126/scisignal.aac6757) 1.Abnormal in wnt signaling -- >90% of sporadic colon tumors 2.Mutation mostly found -- APC (adenomatous polyposis coli) or b-catenin 3.Activation of Fz causes degradation complex releases b-catenin --> b-catenin localize to nucleus 4.b-catenin bind to TCF-4 (transcription factor) --> activate the transcription corresponding to this TF 5.RNF43 involves with DNA-damage response This paper points out three key previous findings; 1.RNF43 is tumor suppressor by reducing the abundance of Fz at plasma mb, thereby, reducing the wnt signaling. 2.Conversely, RNF43 is found at the nucleus envelope, ER and nucleoplasm --> but related to the evidence showing that RNF43 is related to DNA damage response. 3.RNF43 oncogene? or RNF43 tumor suppressor? --> numbers of research, lately, showed it might be tumo...
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My note on paper: Aberrant Wnt/beta-catenin signaling can induce chromosomal instability in colon cancer

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Paper: Aberrant Wnt/beta-catenin signaling can induce chromosomal instability in colon cancer (doi:10.1073/pnas.0604206103) Abstract: Chromosomal instability (CIN+) 1. hallmark of most colon tumors 2. promote tumor progression by increasing rate of genetic aberration 3. occur from mitosis/spindle checkpoint defect Gap: Molecular mechanism is unk Rational: 1. colon cancer develop majorly from mutation of APC (Anaphase-promoting complex) 2. malfunction of APC causes wnt/b-catenin activation --> activate conductin/AXIN2 Research results: 1.wnt/catenin activation causes CIN via up-regulation of conductin 2.human colon cancer with CIN - found conductin higher 3.conductin is higher during the mitosis 4.conductin is localized with mitotic spindle of colon cancer cells 5.conductin binds polo-like kinase 1 6.when APC is forcibly downreglated by iRNA - conductin is ectopic upregulated lead to CIN in chromosomal stable colon cancer 7.higher expression of conductin di...
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My note on paper: Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas

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Paper: Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas (doi:10.1053/j.gastro.2013.10.045) colon polyps (sessile or traditional serrated adenomas) ------------------------ Research gap: genetic factor that facilitating the colon polyps. Evident: SSA - contain BRAF or KRAS mutation early in development - mutation causes oncogene-induced senescence (OIS) of the intestinal crypt cell - escape from OIS facilitates the development of serrated neoplasia by inactivating of tumor suppressor Aim: Investigate subject having SSA contains germline loss of function mutation (nonsense and splice site) in gene regulate the OIS (p16-Rb and ATM-ATR) -- cause the transition from OIS to SSA Method: 1.Bioinformatics reveal set of gene function in the main node of p16-Rb and ATM-ATR dna damage response pw 2.Whole-exosome sequencing on multiple SSA (compare SSA (20 cases) vs control group with same ethnicity) 3.Integrative ...
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