Overexpression of GPR35 confers drug resistance in NSCLC cells by &amp;beta;-arrestin/Akt signaling

Wang, Wei; Han, Tianci; Tong, Wei; Zhao, Jian; Qiu, Xueshan

doi:10.2147/ott.s175606

Cited by 25 publications

(21 citation statements)

References 34 publications

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“…In the present study, the expression levels of CXCL17 and CXCR8 were higher in colon cancer tissues compared with healthy tumour-adjacent tissues. This finding was consistent with previous studies on CXCL17 in colon cancer (8), as well as CXCR8 in breast cancer (15) and lung cancer (19). Recent studies performed at the mRNA level suggested that both CXCL17 (20) and CXCR8 (21) were ectopically expressed in primary colon cancer tissues and regional positive lymph nodes.…”

Section: Discussionsupporting

confidence: 92%

“…A recent study revealed that CXCL17 in HCC mediates the invasion of malignant cells (22). In addition, high GPR35 expression correlates with drug resistance in lung cancer (19). Compared with studies on other malignancies, high CXCL17 and CXCR8 expression in the present study was associated with different outcomes, as patients with high expression had an improved prognosis.…”

Section: Genecontrasting

confidence: 59%

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Prognostic value of CXCL17 and CXCR8 expression in patients with colon cancer

Yao

Bai

et al. 2020

Oncol Lett

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C-X-C motif chemokine ligand 17 (CXCL17) is a mucous chemokine and its expression is highly correlated with that of G protein-coupled receptor 35 (GPR35), which has been confirmed as its receptor and named C-X-C motif chemokine receptor 8 (CXCR8). CXCL17 is upregulated in several types of cancer. However, the biological role of this chemokine in colon cancer remains unknown. In the present study, the expression levels of CXCL17 and CXCR8 were examined using immunohistochemistry in 101 colon cancer tissues and 79 healthy tumour-adjacent tissues. CXCL17 and CXCR8 expression levels were increased in the colon cancer samples compared with tumour-adjacent samples. Patients with high CXCL17 expression had longer overall survival (OS) compared with patients with low expression of CXCL17 (log-rank test; P=0.027). However, CXCR8 expression, but not CXCL17, was an independent prognostic factor for OS in patients with colon cancer. The expression of CXCR8 correlated positively with that of CXCL17 in colon cancer samples (ρ=0.295; P=0.003). Furthermore, the combined high expression of CXCL17 and CXCR8 was a significant independent prognostic factor for OS in patients with colon cancer (P=0.001). In subgroups with a TNM stage of I-II, the patients with combined high expression of CXCL17 and CXCR8 had a longer survival compared with those without combined high expression (P=0.001). However, this difference was not observed in subgroups with a TNM stage of III-IV. Collectively, these findings suggest that CXCL17/CXCR8 signalling may be involved in colon cancer and contribute to improved patient outcomes.

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Section: Discussionsupporting

confidence: 92%

Section: Genecontrasting

confidence: 59%

Prognostic value of CXCL17 and CXCR8 expression in patients with colon cancer

Yao

Bai

et al. 2020

Oncol Lett

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“…GPR35 protein expression was significantly elevated in primary tumour tissue of non-small-cell lung cancer as compared to normal lung, and high expression levels correlated with poor prognosis. 27 In contrast, although GPR35 protein expression in breast cancer primary tumours was increased, it did not correlate with poor prognosis. 10 Our results in CC primary tumours are similar to those in breast cancer.…”

Section: Discussionmentioning

confidence: 91%

Utility of G protein-coupled receptor 35 expression for predicting outcome in colon cancer

et al. 2019

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The utility of mRNA and protein determinations of G protein-coupled receptor 35, that is, GPR35a (GPR35 V1) and GPR35b (GPR35 V2/3), as indicators of outcome for colon cancer patients after curative surgery was investigated. Expression levels of V1 and V2/3 GPR35, carcinoembryonic antigen and CXCL17 mRNAs were assessed in primary tumours and regional lymph nodes of 121 colon cancer patients (stage I–IV), colon cancer cell lines and control colon epithelial cells using real-time quantitative reverse transcriptase-polymerase chain reaction. Expression of G protein-coupled receptor 35 was investigated by two-colour immunohistochemistry and immunomorphometry. GPR35 V2/3 mRNA, but not V1 mRNA, was expressed in colon cancer cell lines, primary colon tumours and control colon epithelial cells. Haematoxylin and eosin positive (H&E(+)), but not H&E(–), lymph nodes expressed high levels of GPR35 V2/3 mRNA ( P<0.0001). GPR35b and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer tumour cells. Kaplan–Meier and hazard ratio analysis revealed that patients with lymph nodes expressing high levels of GPR35 V2/3 mRNA and, in particular, in the group of patients with lymph nodes also expressing carcinoembryonic antigen mRNA, had a short disease-free survival time, 67 months versus 122 months at 12-year follow-up (difference: 55 months, P = 0.001; hazard ratio: 3.6, P = 0.002). In conclusion, high level expression of G protein-coupled receptor 35 V2/3 mRNA in regional lymph nodes of colon cancer patients is a sign of poor prognosis.

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“… 7 In nonsmall cell lung cancer (NSCLC), overexpression of GPR35 is associated with poor prognosis in patients, and GPR35 knockdown significantly overcomes chemoresistance in NSCLC in vitro and in vivo . 55 Such data imply that GPR35 may facilitate cancer growth and metastasis and, potentially, serve as a clinical tumor marker. It is, therefore, of considerable interest to investigate the significance, signaling and function of GPR35 in late stages of cancers more fully.…”

Section: Potential Therapeutic Opportunitiesmentioning

confidence: 99%

Therapeutic Opportunities and Challenges in Targeting the Orphan G Protein-Coupled Receptor GPR35

Quon

Lin

Ganguly

et al. 2020

ACS Pharmacol. Transl. Sci.

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GPR35 is a class A, rhodopsin-like G protein-coupled receptor (GPCR) first identified more than 20 years ago. In the intervening period, identification of strong expression in the lower intestine and colon, in a variety of immune cells including monocytes and a variety of dendritic cells, and in dorsal root ganglia has suggested potential therapeutic opportunities in targeting this receptor in a range of conditions. GPR35 is, however, unusual in a variety of ways that challenge routes to translation. These include the following: (i) Although a substantial range and diversity of endogenous ligands have been suggested as agonist partners for this receptor, it officially remains defined as an “orphan” GPCR. (ii) Humans express two distinct protein isoform sequences, while rodents express only a single form. (iii) The pharmacologies of the human and rodent orthologues of GPR35 are very distinct, with variation between rat and mouse GPR35 being as marked as that between either of these species and the human forms. Herein we provide perspectives on each of the topics above as well as suggesting ways to overcome the challenges currently hindering potential translation. These include a better understanding of the extent and molecular basis for species selective GPR35 pharmacology and the production of novel mouse models in which both “on-target” and “off-target” effects of presumptive GPR35 ligands can be better defined, as well as a clear understanding of the human isoform expression profile and its significance at both tissue and individual cell levels.

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Overexpression of GPR35 confers drug resistance in NSCLC cells by β-arrestin/Akt signaling

Cited by 25 publications

References 34 publications

Prognostic value of CXCL17 and CXCR8 expression in patients with colon cancer

Prognostic value of CXCL17 and CXCR8 expression in patients with colon cancer

Utility of G protein-coupled receptor 35 expression for predicting outcome in colon cancer

Therapeutic Opportunities and Challenges in Targeting the Orphan G Protein-Coupled Receptor GPR35

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