General Information of the Molecule (ID: Mol00657)
Name
Serine/threonine-protein kinase 4 (MST1) ,Homo sapiens
Synonyms
Mammalian STE20-like protein kinase 1; MST-1; STE20-like kinase MST1; Serine/threonine-protein kinase Krs-2; MST1/N; MST1/C; KRS2; MST1
    Click to Show/Hide
Molecule Type
Protein
Gene Name
STK4
Gene ID
6789
Location
chr20:44966479-45080021[+]
Sequence
METVQLRNPPRRQLKKLDEDSLTKQPEEVFDVLEKLGEGSYGSVYKAIHKETGQIVAIKQ
VPVESDLQEIIKEISIMQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKT
LTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAK
RNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNP
PPTFRKPELWSDNFTDFVKQCLVKSPEQRATATQLLQHPFVRSAKGVSILRDLINEAMDV
KLKRQESQQREVDQDDEENSEEDEMDSGTMVRAVGDEMGTVRVASTMTDGANTMIEHDDT
LPSQLGTMVINAEDEEEEGTMKRRDETMQPAKPSFLEYFEQKEKENQINSFGKSVPGPLK
NSSDWKIPQDGDYEFLKSWTVEDLQKRLLALDPMMEQEIEEIRQKYQSKRQPILDAIEAK
KRRQQNF
    Click to Show/Hide
Function
Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.
    Click to Show/Hide
Uniprot ID
STK4_HUMAN
Ensembl ID
ENSG00000101109
HGNC ID
HGNC:11408
        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)
4 drug(s) in total
Click to Show/Hide the Full List of Drugs
Cisplatin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Ovarian cancer [1]
Resistant Disease Ovarian cancer [ICD-11: 2C73.0]
Resistant Drug Cisplatin
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Hippo signaling pathway Inhibition hsa04390
In Vitro Model SkOV3 cells Ovary Homo sapiens (Human) CVCL_0532
A2780 cells Ovary Homo sapiens (Human) CVCL_0134
OVCAR3 cells Ovary Homo sapiens (Human) CVCL_0465
HO8910 cells Ovary Homo sapiens (Human) CVCL_6868
CAOV3 cells Ovary Homo sapiens (Human) CVCL_0201
ES-2 cells Ovary Homo sapiens (Human) CVCL_3509
TOV-21G cells Ovary Homo sapiens (Human) CVCL_3613
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description miR-149-5p promotes the chemoresistance of ovarian cancer cells by directly targeting MST1 and SAV1, leading to the inactivation of Hippo signaling.
Fluorouracil
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Pancreatic cancer [2]
Resistant Disease Pancreatic cancer [ICD-11: 2C10.3]
Resistant Drug Fluorouracil
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Hippo signaling pathway Regulation hsa04392
In Vitro Model BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
PANC-1 cells Pancreas Homo sapiens (Human) CVCL_0480
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Gemcitabine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
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
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Hippo signaling pathway Regulation hsa04392
In Vitro Model BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
PANC-1 cells Pancreas Homo sapiens (Human) CVCL_0480
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Paclitaxel
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Pancreatic cancer [2]
Resistant Disease Pancreatic cancer [ICD-11: 2C10.3]
Resistant Drug Paclitaxel
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Hippo signaling pathway Regulation hsa04392
In Vitro Model BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
PANC-1 cells Pancreas Homo sapiens (Human) CVCL_0480
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
Click to Show/Hide the Resistance Disease of This Class
Pancreatic cancer [ICD-11: 2C10]
Click to Show/Hide
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: 7.18E-01; Fold-change: 4.31E-01; Z-score: 3.73E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 7.20E-03; Fold-change: 6.64E-01; Z-score: 6.32E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Ovarian cancer [ICD-11: 2C73]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Ovary
The Specified Disease Ovarian cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 3.44E-03; Fold-change: 3.70E-01; Z-score: 1.41E+00
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 5.36E-03; Fold-change: -5.23E-01; Z-score: -1.00E+00
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Tissue-specific Molecule Abundances in Healthy Individuals
Click to Show/Hide the Molecule Abundances
References
Ref 1 miR 149 5p promotes chemotherapeutic resistance in ovarian cancer via the inactivation of the Hippo signaling pathway. Int J Oncol. 2018 Mar;52(3):815-827. doi: 10.3892/ijo.2018.4252. Epub 2018 Jan 24.
Ref 2 Upregulation of miR-181c contributes to chemoresistance in pancreatic cancer by inactivating the Hippo signaling pathway. Oncotarget. 2015 Dec 29;6(42):44466-79. doi: 10.18632/oncotarget.6298.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Zhang.