Molecule Information

General Information of the Molecule (ID: Mol00159)

• Name: SHC-transforming protein 1 (SHC1) ,Homo sapiens
• Synonyms: SHC-transforming protein 3; SHC-transforming protein A; Src homology 2 domain-containing-transforming protein C1; SH2 domain protein C1; SHC; SHCA
• Molecule Type: Protein
• Gene Name: SHC1
• Gene ID: 6464
• Location: chr1:154962298-154974395[-]
• Sequence:
  MDLLPPKPKYNPLRNESLSSLEEGASGSTPPEELPSPSASSLGPILPPLPGDDSPTTLCS
  FFPRMSNLRLANPAGGRPGSKGEPGRAADDGEGIVGAAMPDSGPLPLLQDMNKLSGGGGR
  RTRVEGGQLGGEEWTRHGSFVNKPTRGWLHPNDKVMGPGVSYLVRYMGCVEVLQSMRALD
  FNTRTQVTREAISLVCEAVPGAKGATRRRKPCSRPLSSILGRSNLKFAGMPITLTVSTSS
  LNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKDPVNQRACHILECPEGLAQDV
  ISTIGQAFELRFKQYLRNPPKLVTPHDRMAGFDGSAWDEEEEEPPDHQYYNDFPGKEPPL
  GGVVDMRLREGAAPGAARPTAPNAQTPSHLGATLPVGQPVGGDPEVRKQMPPPPPCPGRE
  LFDDPSYVNVQNLDKARQAVGGAGPPNPAINGSAPRDLFDMKPFEDALRVPPPPQSVSMA
  EQLRGEPWFHGKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEG
  VVRTKDHRFESVSHLISYHMDNHLPIISAGSELCLQQPVERKL
• Function: Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis.
• Uniprot ID: SHC1_HUMAN
• Ensembl ID: ENSG00000160691
• HGNC ID: HGNC:10840

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [1]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: p53/p66shc signaling pathway; Activation; hsa04115
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/DDP cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis
• Mechanism Description: Downregulated long non-coding RNA TRPM2-AS inhibits cisplatin resistance of non-small cell lung cancer cells via activation of p53- p66shc pathway.

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Pancreatic cancer [2]

• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: AsPC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0152
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-365 directly targets the pro-apoptotic molecules SHC1 and BAX, whose reductions contribute to gemcitabine resistance in pancreatic cancer cells.

Idebenone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Nonalcoholic fatty liver disease [3]

• Resistant Disease: Nonalcoholic fatty liver disease [ICD-11: DB92.0]
• Resistant Drug: Idebenone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Fast food diet (FFD) mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Glucose tolerance test (GTT); Insulin tolerance test (ITT)
• Mechanism Description: In the metabolic FFD model, idebenone administration improved insulin resistance, and reduced inflammation and fibrosis shown with qPCR, hydroxyproline measurement, and histology.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Pancreatic cancer [ICD-11: 2C10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Pancreas
• The Specified Disease: Pancreatic cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.28E-03; Fold-change: 3.13E-01; Z-score: 5.54E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.28E-04; Fold-change: 6.00E-01; Z-score: 8.28E-01

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.14E-04; Fold-change: 6.00E-02; Z-score: 1.55E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.13E-01; Fold-change: -1.53E-01; Z-score: -3.22E-01

ICD Disease Classification 13

Nonalcoholic fatty liver disease [ICD-11: DB92]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Nonalcoholic fatty liver disease
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.27E-01; Fold-change: 1.14E-01; Z-score: 5.38E-01

References

• Ref 1: Downregulated long non-coding RNA TRPM2-AS inhibits cisplatin resistance of non-small cell lung cancer cells via activation of p53- p66shc pathway. Eur Rev Med Pharmacol Sci. 2017 Jun;21(11):2626-2634.
• Ref 2: MiR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX. Cell Signal. 2014 Feb;26(2):179-85. doi: 10.1016/j.cellsig.2013.11.003. Epub 2013 Nov 9.
• Ref 3: Shc inhibitor idebenone ameliorates liver injury and fibrosis in dietary NASH in mice .J Biochem Mol Toxicol. 2021 Oct;35(10):e22876. doi: 10.1002/jbt.22876. Epub 2021 Aug 8. 10.1002/jbt.22876