Last update 01 Nov 2024

STAT3 x SHP1

Last update 01 Nov 2024

Basic Info

Related Targets

STAT3SHP1

Drugs associated with STAT3 x SHP1

SC-59

Target

SHP1 x STAT3

Mechanism

SHP1 agonists [+1]

Active Org.

National Taiwan University

Originator Org.

National Taiwan University

Active Indication

Hepatocellular Carcinoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SC-60

Target

SHP1 x STAT3

Mechanism

SHP1 agonists [+1]

Active Org.-

Originator Org.

National Taiwan University

Active Indication-

Inactive Indication

Hepatocellular Carcinoma

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with STAT3 x SHP1

100 Translational Medicine associated with STAT3 x SHP1

0 Patents (Medical) associated with STAT3 x SHP1

236

Literatures (Medical) associated with STAT3 x SHP1

01 Sep 2024·IUBMB Life

Kaempferide triggers apoptosis and paraptosis in pancreatic tumor cells by modulating the ROS production, SHP‐1 expression, and the STAT3 pathway

Article

Author: Bastos, Jairo Kenupp ; Ahn, Kwang Seok ; Jung, Young Yun ; Luyen, Nguyen Dinh ; Huong, Le Mai ; Mohan, Chakrabhavi Dhananjaya ; Son, Ninh The

AbstractPancreatic cancer is one of the deadliest diseases with a poor prognosis and a five‐survival rate. The STAT3 pathway is hyperactivated which contributes to the sustained proliferative signals in pancreatic cancer cells. We have isolated kaempferide (KF), an O‐methylated flavonol, from the green propolis of Mimosa tenuiflora and examined its effect on two forms of cell death namely, apoptosis and paraptosis. KF significantly increased the cleavage of caspase‐3 and PARP. It also downmodulated the expression of Alix (an intracellular inhibitor of paraptosis) and increased the expression of CHOP and ATF4 (transcription factors that promote paraptosis) indicating that KF promotes apoptosis as well as paraptosis. KF also increased intracellular reactive oxygen species (ROS) suggesting the perturbance of the redox state. N‐acetylcysteine reverted the apoptosis‐ and paraptosis‐inducing effects of KF. Some ROS inducers are known to suppress the STAT3 pathway and investigation revealed that KF downmodulates STAT3 and its upstream kinases (JAK1, JAK2, and Src). Additionally, KF also elevated the expression of SHP‐1, a tyrosine phosphatase which is involved in the negative modulation of the STAT3 pathway. Knockdown of SHP‐1 prevented KF‐driven STAT3 inhibition. Altogether, KF has been identified as a promoter of apoptosis and paraptosis in pancreatic cancer cells through the elevation of ROS generation and SHP‐1 expression.

01 Sep 2024·Journal of Advanced Research

Leucine zipper protein 1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling

Article

Author: Jiang, Wan-Li ; Fan, Yong-Zhen ; Liu, Hui-Xia ; He, Tao ; Chen, Ming ; Lu, Zhi-Bing ; Peng, Li ; Cao, Jian-Lei ; Zhang, Wei ; Jin, Zhi-Li ; Wang, Hai-Rong ; Li, Yi ; Fan, Di ; Wu, Xiao-Yan ; He, Bo ; Yu, Wen-Xi ; Hu, Xiao-Rong

INTRODUCTIONCardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive.OBJECTIVESThis study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach.METHODSCardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro.RESULTSLUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro.CONCLUSIONWe demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy.

01 Apr 2024·Biochemical and Biophysical Research Communications

Natural compound Byakangelicin suppresses breast tumor growth and motility by regulating SHP-1/JAK2/STAT3 signal pathway

Article

Author: Lai, Yuexing ; Cang, Yanqin ; Liu, Wenjing ; Shi, Xiuzhen ; Zhang, Xi

Byakangelicin mostly obtained from the root of Angelica dahurica and has protective effect on liver injury and fibrosis. In addition, Byakangelicin, as a traditional medicine, is also used to treat colds, headache and toothache. Recent studies have shown that Byakangelicin exhibits anti-tumor function; however, the role of Byakangelicin in breast tumor progression and related mechanism has not yet been elucidated. Our study aims to investigate the role of Byakangelicin in breast tumor progression and the underlying mechanism. To measure the effect of Byakangelicin on JAK2/STAT3 signaling, a dual luciferase reporter assay and a Western blot assay were performed. CCK8, colony formation, apoptosis and cell invasion assays were used to examine the inhibitory potential of Byakangelicin on breast cancer cells. Additionally, SHP-1 was silenced by specific siRNA duplex and the function of SHP-1 on Byakangelicin-mediated inhibition of JAK2/STAT3 signaling was evaluated. Byakangelicin treatment significantly inhibited STAT3 transcriptional activity. In addition, Byakangelicin treatment blocked JAK2/STAT3 signaling in a dose-dependent manner. Byakangelicin-treated tumor cells showed a dramatically reduced proliferation, colony formation and invasion ability. Moreover, Byakangelicin remarkedly induced breast cancer cell apoptosis. Furthermore, Byakangelicin regulated the expression of SHP1.In conclusion, our current study indicated that Byakangelicin, a natural compound, inhibits SHP-1/JAK2/STAT3 signaling and thus blocks tumor growth and motility.

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