Sequential combination of docetaxel with a SHP-1 agonist enhanced suppression of p-STAT3 signaling and apoptosis in triple negative breast cancer cells

Liu, Chun Yu; Chen, Kuen Feng; Chao, Tzu I.; Chu, Pei Yi; Huang, Chun Yao; Huang, Tzu Ting; Yang, Hsiu Ping; Wang, Wan-Lun; Lee, Chia-Han; Lau, Ka Yi; Tsai, Wen Chun; Su, Jun-Ming; Wu, Chia Yun; Chen, Ming-Huang; Shiau, Chung Wai; Tseng, Ling Ming

doi:10.1007/s00109-017-1549-x

Cited by 18 publications

(13 citation statements)

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“…SHP-1, which is expressed in hematopoietic and epithelial cells, is a PTP that antagonizes the growth-promoting and oncogenic potential of tyrosine kinases 29 . SHP-1 has been proposed as a candidate tumor suppressor gene in prostate cancer, hepatocellular carcinoma, and other cancers [29][30][31][32] . The clinical relevance of SHP-1 in breast cancer remains unclear.…”

Section: Discussionmentioning

confidence: 99%

SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer

Geng

Xian

et al. 2021

Cancer Biol Med

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Objective:The aims of this study were to examine the prognostic value of SHP-1 in breast cancer, its roles in the regulation of breast cancer cell growth and metastasis, and the underlying mechanisms. Methods: Tumor specimens from 160 patients with breast cancer and 160 noncancerous tissues were used to examine the expression of SHP-1 and to analyze its association with overall survival through Kaplan-Meier and multivariate Cox regression analyses. RNA sequencing data and the expression and clinical importance of SHP-1 in breast cancer were evaluated with data from The Cancer Genome Atlas. In vitro and in vivo assays were performed to elucidate the effects of SHP-1 on breast cancer cell proliferation and invasion. Confocal immunofluorescence and GST pulldown assays were used to demonstrate the interaction between SHP-1 and epidermal growth factor receptor, as well as its downstream pathways. Immunohistochemistry and The Cancer Genome Atlas database were used to investigate the clinical association between SHP-1 and EGFR in human breast cancer. Results: SHP-1 expression was associated with better survival in patients with breast cancer, whereas SHP-1 expression was negatively correlated with EGFR in human breast cancer. Ectopic SHP-1 expression significantly suppressed breast cancer cell proliferation, migration, and invasion. SHP-1 knockdown induced a more invasive phenotype and accelerated cell growth. Mechanistically, EGFR, a protein directly interacting with SHP-1, mediates the SHP-1-induced inactivation of Ras/Erk/GSK3β signaling and its downstream effectors. Conclusions: SHP-1 is an important prognostic biomarker in patients with breast cancer, and the SHP-1-EGFR axis is a promising target for treatment.

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Section: Discussionmentioning

confidence: 99%

SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer

Geng

Xian

et al. 2021

Cancer Biol Med

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“…SHP-1/p-STAT3/VEGF-A axis is a potential therapeutic target for metastatic TNBC, and the more potent SC-78 may be a promising lead for suppressing metastasis of TNBC [33]. Sequential combination of do-cetaxel with a SHP-1 agonist enhanced suppression of p-STAT3 signaling and apoptosis in triple negative breast cancer cells [34]. Targeting SHP-1/p-STAT3 and the potential combination of SHP-1 agonist with chemotherapeutic docetaxel is a feasible therapeutic strategy for TNBC [35].…”

Section: Discussionmentioning

confidence: 99%

Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression

et al. 2021

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This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.

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“…Another sorafenib analogue, SC-43, was reported to block STAT3 signaling to increase the sensitivity of cancer cells to chemotherapeutic drugs like docetaxel. SC-43 showed tumor growth inhibition and apoptosis inducing by suppressing the SHP-1-dependent STAT3 expression [ 100 ]. SG-1721, a (-)-galiellalactone analogue, was found to inhibit the growth of TNBC cells.…”

Section: Targeting Apoptotic Pathways With Small-molecule Compounds I...mentioning

confidence: 99%

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

et al. 2022

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Triple-negative breast cancer (TNBC) is a subtype of human breast cancer with one of the worst prognoses, with no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed cell death (PCD), has been widely reported to have numerous links to the progression and therapy of many types of human cancer. Of note, RCD can be divided into numerous different subroutines, including autophagy-dependent cell death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis and anoikis. More recently, targeting the subroutines of RCD with small-molecule compounds has been emerging as a promising therapeutic strategy, which has rapidly progressed in the treatment of TNBC. Therefore, in this review, we focus on summarizing the molecular mechanisms of the above-mentioned seven major RCD subroutines related to TNBC and the latest progress of small-molecule compounds targeting different RCD subroutines. Moreover, we further discuss the combined strategies of one drug (e.g., narciclasine) or more drugs (e.g., torin-1 combined with chloroquine) to achieve the therapeutic potential on TNBC by regulating RCD subroutines. More importantly, we demonstrate several small-molecule compounds (e.g., ONC201 and NCT03733119) by targeting the subroutines of RCD in TNBC clinical trials. Taken together, these findings will provide a clue on illuminating more actionable low-hanging-fruit druggable targets and candidate small-molecule drugs for potential RCD-related TNBC therapies. Graphical abstract

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Sequential combination of docetaxel with a SHP-1 agonist enhanced suppression of p-STAT3 signaling and apoptosis in triple negative breast cancer cells

Cited by 18 publications

References 47 publications

SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer

SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer

Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

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