Downregulation of the Unfolded Protein Response Links Metformin Treatment to Good Clinical Outcomes in Colorectal Cancer Patients.
Type 2 diabetes is a risk factor for colorectal cancer (CRC) development and progression. However, metformin-treated diabetic CRC patients tend to have better clinical outcomes than those managed by other means. To better characterize the molecular underpinnings of metformin's protective effects, we...
| Publicado en: | Current Oncology Vol. 32; no. 3; pp. 138 - 160 |
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| Autores principales: | , , , , , , |
| Formato: | Journal Article |
| Publicado: |
MDPI
Mar2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=184100036&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 184100036 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11980052 5EKK jtl: Current Oncology issn: 11980052 maglogo: N pubinfo: dt: Mar2025 vid: 32 iid: 3 pid: 97109 pub: MDPI artinfo: ui: 184100036 10.3390/curroncol32030138 184100036 ppf: 138 ppct: 22 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Downregulation of the Unfolded Protein Response Links Metformin Treatment to Good Clinical Outcomes in Colorectal Cancer Patients. aug: au: Fay, Mary L. Nicol, Chris Orr, Christine Wilson, Brooke Hurlbut, David Feilotter, Harriet Davey, Scott affil: Division of Cancer Biology and Genetics, Sinclair Cancer Research Institute at Queen's University, Kingston, ON K7L 3N6, Canada sug: ab: Type 2 diabetes is a risk factor for colorectal cancer (CRC) development and progression. However, metformin-treated diabetic CRC patients tend to have better clinical outcomes than those managed by other means. To better characterize the molecular underpinnings of metformin's protective effects, we performed a targeted transcriptomic analysis of primary CRC tissue samples (n = 272). A supervised learning algorithm pinpointed molecular features that discriminate between metformin-treated and diet-controlled diabetic CRC samples, as well as those that discriminated between non-diabetic samples based on their five-year overall survival status. Our results show downregulation of TMEM132 in metformin-treated samples (p = 0.05) and non-diabetics with good clinical outcomes (p = 0.05) relative to diet-controlled and non-diabetics with poor survival, respectively. Furthermore, upregulation of SCNN1A is observed in metformin-treated samples (p = 0.04) and non-diabetics with good clinical outcomes (p = 0.01) relative to diet-controlled samples and those with poor clinical outcomes, respectively. We also show that the antiapoptotic protein sFas is downregulated in metformin-treated samples relative to diet-controlled samples (p = 0.005). These findings suggest a role for the unfolded protein response in mediating metformin-related CRC-protective effects by enhancing apoptosis and suggest the investigation of these proteins as targets for novel CRC therapies. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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