Molecule Information

General Information of the Molecule (ID: Mol04405)

Name	Transcription factor HES-1 (HES1) ,Homo sapiens
Synonyms	Class B basic helix-loop-helix protein 39; Hairy and enhancer of split 1; Hairy homolog; Hairy-like protein Click to Show/Hide
Molecule Type	Protein
Gene Name	HES1
Gene ID	3280
Sequence	MPADIMEKNSSSPVAATPASVNTTPDKPKTASEHRKSSKPIMEKRRRARINESLSQLKTL ILDALKKDSSRHSKLEKADILEMTVKHLRNLQRAQMTAALSTDPSVLGKYRAGFSECMN E VTRFLSTCEGVNTEVRTRLLGHLANCMTQINAMTYPGQPHPALQAPPPPPPGPGGPQH AP FAPPPPLVPIPGGAAPPPGGAPCKLGSQAGEAAKVFGGFQVVPAPDGQFAFLIPNGA FAH SGPVIPVYTSNSGTSVGPNAVSPSSGPSLTADSMWRPWRN Click to Show/Hide
Function	Transcriptional repressor of genes that require a bHLHprotein for their transcription. May act as a negative regulator ofmyogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA onN-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity . May play a role in afunctional FA core complex response to DNA cross-link damage, beingrequired for the stability and nuclear localization of FA core complexproteins, as well as for FANCD2 monoubiquitination in response to DNAdamage. {ECO:0000250, ECO:0000269\|PubMed:18550849}. Click to Show/Hide
Uniprot ID	HES1_HUMAN
Ensembl ID	ENSG000001143154
HGNC ID	HGNC:5192
*Click to Show/Hide the Complete Species Lineage*
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)

1 drug(s) in total

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Eribulin

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1]				[1]
Resistant Disease	Breast adenocarcinoma [ICD-11: 2C60.1]			Disease Info
Resistant Drug	Eribulin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Notch signaling pathway		Activation	hsa04330
	JAK-STAT signaling pathway		Activation	hsa04630
In Vitro Model	MCF-7 ER cells	Breast	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blot assay
Experiment for Drug Resistance	Annexin V/PI assay; MTT assay
Mechanism Description	We confirmed that BYL-719 could inhibit BCSC-like cell proliferation in 3D cultures and that the stemness characteristics of BCSC-like cells were inhibited. The PI3K/AKT/mTOR signaling pathway could be inhibited by BYL-719, and the Notch, JAK-STAT and MAPK/ERK signaling pathways which have crosstalk in the tumor microenvironment (TME) are also inhibited. By comparing eribulin-resistant breast cancer cell lines, we confirmed that BYL-719 could effectively overcome drug resistance.

References

Ref 1	Effects of BYL-719 (alpelisib) on human breast cancer stem cells to overcome drug resistance in human breast cancer. Front Pharmacol. 2024 Oct 14;15:1443422.