Low folate metabolic stress reprograms DNA methylation‐activated sonic hedgehog signaling to mediate cancer stem cell‐like signatures and invasive tumour stage‐specific malignancy of human colorectal cancers

The mechanistic role of colonic low folate metabolic stress (LFMS) in colorectal cancer (CRC) malignancy development remains unknown. Folate analysis on the 99 paired human CRC tissues localized LFMS to the deep invasive T3/T4 staged tumours with hypo‐methylated sonic hedgehog (Shh) promoter region...

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Veröffentlicht in:	International journal of cancer 2017-12, Vol.141 (12), p.2537-2550
Hauptverfasser:	Feng, Hsin‐Chun, Lin, Jhuan‐Yu, Hsu, Shu‐Han, Lan, Wen‐Yu, Kuo, Chang‐Sheng, Tian, Yu‐Feng, Sun, Ding‐Ping, Huang, Rwei‐Fen Syu
Format:	Artikel
Sprache:	eng
Schlagworte:	Adenocarcinoma Cancer cancer stem cell Carcinogenesis Cell Line, Tumor Cell self-renewal Chemotherapy Colon Colon cancer Colorectal cancer colorectal cancer invasion Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Deoxyribonucleic acid Deregulation DNA DNA Methylation E-cadherin Epithelial-Mesenchymal Transition Female Folic acid Folic Acid - metabolism Gelatinase A Gelatinase B Gene Expression Regulation, Neoplastic Genotypes Hedgehog protein Hedgehog Proteins - genetics Humans Invasiveness low folate metabolic stress Male Malignancy Matrix protein Medical research Mesenchyme Metabolism Metastases Methylation Neoplastic Stem Cells - metabolism Oct-4 protein Oxidative stress Pluripotency Promoter Regions, Genetic Signal Transduction sonic hedgehog signal Spurs Stem cells Stress Stress, Physiological Tissues Transcription Tumors Vitamin B Zinc Finger Protein GLI1 - genetics
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Zusammenfassung:	The mechanistic role of colonic low folate metabolic stress (LFMS) in colorectal cancer (CRC) malignancy development remains unknown. Folate analysis on the 99 paired human CRC tissues localized LFMS to the deep invasive T3/T4 staged tumours with hypo‐methylated sonic hedgehog (Shh) promoter region and amplified expressions of Shh ligand and Gli1 effector, which coincided with deregulated expressions of the epithelial‐mesenchymal transition (EMT) mediators. Colonic folate levels of CRC were inversely correlated with pluripotent expressions of the SOX2, NANOG and OCT4 markers (p
ISSN:	0020-7136 1097-0215
DOI:	10.1002/ijc.31008