Role of ROR2 in promoting gastric cancer metastasis by enhancing c-JUN-mediated MMP3 transcription

Ge, Xiaoxiao; Lin, Feng; Wu, Zheng; Lin, Ying; Tang, Wenbo; McKay, Michael J.; Sahu, Arvind; Lino‐Silva, Leonardo S.; Tseng, Joshua; Li, Jin

doi:10.21037/atm-22-4583

Cited by 6 publications

(3 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, our data point to a pro-tumorigenic function of ROR2 in PDAC, which is consistent with previous findings in melanoma, gastric or breast cancer, where it was shown to regulate cancer cell aggressiveness, including proliferation, stemness and EMT (Castro et al, 2023;Ge et al, 2022;Menck et al, 2021;O'Connell et al, 2010). However, it can also play tumor-suppressive roles, such as inhibition of invasion and metastasis, as is seen in prostate and endometrial cancer, suggesting that ROR2's function needs to be carefully evaluated in each cancer type before considering its role as a potential therapeutic target (Liu et al, 2021;Tseng et al, 2020).…”

Section: Discussionsupporting

confidence: 92%

ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma

Benitz,

Steep,

Nasser

et al. 2024

Cancer Discovery

View full text Add to dashboard Cite

Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor Pdx1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in mouse and human. We have identified the receptor tyrosine kinase Ror2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition.

show abstract

Section: Discussionsupporting

confidence: 92%

ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma

Benitz,

Steep,

Nasser

et al. 2024

Cancer Discovery

View full text Add to dashboard Cite

show abstract

“…ROR2 could promote gastric cancer metastasis by enhancing PSMA7c-JUN-mediated MMP3 transcription. [ 21 ] KLK6 could promote cell growth, migration, and invasion of STAD. [ 22 ] PSMA1 promoted tumor progression and resulted in poor prognosis in STAD.…”

Section: Discussionmentioning

confidence: 99%

A degradome-related signature for predicting the prognosis and immunotherapy benefit in stomach adenocarcinoma based on machine learning procedure

Deng,

Feng,

Zhao

et al. 2024

Medicine

View full text Add to dashboard Cite

Stomach adenocarcinoma (STAD) is one of the subtype of gastric cancer with high invasiveness, extreme heterogeneity, high morbidity, and high mortality. The degradome is the most abundant class of cellular enzymes that play an essential role in regulating cellular activity and carcinogenesis. An integrative machine learning procedure including 10 methods was performed to develop a prognostic degradome-based prognostic signature (DPS) in TCGA, GSE15459, GSE26253, and GSE62254 datasets. Investigations of the DPS concerning immune infiltration, immunotherapy benefits, and drug priority were orchestrated. The DPS developed by Enet [alpha = 0.3] method was regarded as the optimal prognostic model. The DPS had a stable and powerful performance in predicting the clinical outcome of STAD and served as an independent risk factor in training and testing cohorts. The C-index of DPS was higher than that of age, sex, and clinical stage. STAD patients with low DPS scores had a higher abundance of B cells, CD8+ T cells, higher cytolytic scores, and T cell co-stimulation scores. Moreover, low DPS score indicated a lower tumor immune dysfunction and exclusion score, lower T cell dysfunction and exclusion score, higher PD1&CTLA4 immunophenoscore, and higher tumor mutation burden score in STAD, demonstrating a better immunotherapy response. STAD patients with a high DPS score had a lower IC50 value of common chemotherapy and targeted therapy regimens (Cisplatin, Docetaxel, Gefitinib, etc). Our study developed an optimal DPS for STAD. The DPS could predict the prognosis, risk stratification and guide treatment for STAD patients.

show abstract

“…Fra-1 is a member of the FOS family and is an important nuclear transcription factor that regulates the growth, differentiation, and apoptosis of normal cells [ 6 , 7 , 19 – 21 ]. Fra-1 is highly expressed in a variety of malignant tumors and plays an important role in cell transformation, proliferation, invasion, and metastasis [ 18 – 21 , 35 ]. Our previous study found that Fra-1 was highly expressed in GC tissues compared with that in adjacent non-cancerous tissues.…”

Section: Discussionmentioning

confidence: 99%

YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells

He¹,

Zeng²,

Jin³

et al. 2023

Oncology Research

View full text Add to dashboard Cite

Fos-related antigen 1 (Fra-1) is a nuclear transcription factor that regulates cell growth, differentiation, and apoptosis. It is involved in the proliferation, invasion, apoptosis and epithelial mesenchymal transformation of malignant tumor cells. Fra-1 is highly expressed in gastric cancer (GC), affects the cycle distribution and apoptosis of GC cells, and participates in GC occurrence and development. However, the detailed mechanism of Fra-1 in GC is unclear, such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis. In this study, we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) as a Fra-1-interacting protein in GC cells using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry. Experiments showed that YWHAH positively regulated Fra-1 mRNA and protein expression, and affected GC cell proliferation. Whole proteome analysis showed that Fra-1 affected the activity of the high mobility group AT-hook 1 (HMGA1)/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway in GC cells. Western blotting and flow cytometry confirmed that YWHAH activated HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect GC cell proliferation. These results will help to discover new molecular targets for the early diagnosis, treatment, and prognosis prediction of GC.

show abstract

Role of ROR2 in promoting gastric cancer metastasis by enhancing c-JUN-mediated MMP3 transcription

Cited by 6 publications

References 50 publications

ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma

ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma

A degradome-related signature for predicting the prognosis and immunotherapy benefit in stomach adenocarcinoma based on machine learning procedure

YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells

Contact Info

Product

Resources

About