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The endocrine system
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Although some are identified incidentally on imaging. Most are obviously malignant at presentation with invasion of surrounding organs and metastatic disease. Macroscopically they may display malignant growth features (Figure 18.31) and microscopically the typical appearance of an adenoma are absent with cellular pleomorphism, numerous mitoses, necrosis and invasive growth involving blood vessels and surrounding organs (Figure 18.32). The overall prognosis is poor, it is related to patient age, tumour differentiation, and resection status. The genetic profile of carcinomas is complex and several genetic mechanisms are implicated in their pathogenesis, including cytogenetic changes and overexpression of IGF2, TP53 mutations, CTNNB1 mutations, and ZNRF3 deletions. Disease progression is associated with copy number alterations and whole genome duplication. Several genetic syndromes including Li−Fraumeni syndrome, Lynch syndrome and MEN1 are associated with adrenocortical carcinomas. In southern Brazil a founder mutation in TP53 accounts for the high rate of paediatric adrenocortical carcinomas.
R-spondin family biology and emerging linkages to cancer
Published in Annals of Medicine, 2023
Zhimin He, Jialin Zhang, Jianzhong Ma, Lei Zhao, Xiaodong Jin, Hongbin Li
Recent studies have also discovered some novel molecular mechanisms of RSPOs. By way of illustration, Hao et al. demonstrated that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homolog ring finger 43 (RNF43) had negative roles in Wnt signaling. ZNRF3 is connected with the Wnt receptor complex, and the Wnt signaling is suppressed due to the turnover of FZD and LRP6. Inhibiting ZNRF3 not only enhances Wnt/β-catenin signaling but also interrupts Wnt/planar cell polarity (PCP) signaling [18]. Kazanskaya et al. found that the effect of RSPO2 on the Wnt/β-catenin signaling pathway occurred in DSH/DVL or an upstream level. Besides, there is no combination of RSPO2 and LRP6 or FZD, which speculates that there may be other role factors. The study found that the RSPO gene was commonly expressed with Wnt, and the expression is formed in Wnt → RSPO → Wnt [19].
Role of telomeric RAP1 in radiation sensitivity modulation and its interaction with CSC marker KLF4 in colorectal cancer
Published in International Journal of Radiation Biology, 2020
Kumari Anuja, Madhabananda Kar, Amit Roy Chowdhury, Gauri Shankar, Swatishree Padhi, Souvick Roy, Yusuf Akhter, Arabinda Kumar Rath, Birendranath Banerjee
We have also identified several other residues in KLF4 which are involved in strong hydrophobic interactions with RAP1 and shown in Supplementary Table 2. We have selected all the pair of interactive amino acid residues of KLF4 with RAP1 in docked complex and shown in cartoon structures where the pink color sphere represents KLF4 and green color sphere represents RAP1 respectively Figure 6(d–f). In case of KLF4 as many, as 22 amino acid residues participate in its DNA-binding activity in which six residues are located in ZnF1 domain, nine residues are located in ZnF2 domain and seven are located in ZnF3 domain as shown in Supplementary Figure 3. In this study, major participation of ZnF2 domain of KLF4 in protein–protein interaction with RAP1 positively indicates the interaction between both proteins. Amino acid residues Arg392, Glu395, Phe396 and Lys398 involved in the direct interaction with ZnF2 domain of KLF4 and may form hydrogen bonds with Lys453, His450, Arg449 & Lys428 residues as shown in Figure 6(d–f). This in silico analysis revealed that there is a strong physical interaction is present between the functional sites of both proteins.