TROP2 is epigenetically inactivated and modulates IGF‐1R signalling in lung adenocarcinoma

Lin, Jau Chen; Wu, Yi; Wu, Jing; Lin, Tzu Chieh; Wu, Chen; Chang, Yih‐Leong; Jou, Yuh–Shan; Hong, Tse-Ming; Yang, Pan‐Chyr

doi:10.1002/emmm.201200222

Cited by 89 publications

(133 citation statements)

References 47 publications

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“…They also exhibit better survival rates. Thus, TROP2 overexpression is an important independent marker of prognosis in lung carcinomas.A similar relationship is seen in colorectal carcinomas [4]. Decreased overall survival and increased invasiveness is seen in stage IIB colorectal carcinomas that show upregulation of TROP2.…”

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confidence: 62%

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TROP2 expression and its evolving role in tumor pathogenesis in systemic tumors

Kapoor¹

2012

Tumor Biol.

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may play a major role in tumor pathogenesis in a number of systemic malignancies.Pulmonary squamous cell carcinomas tend to show increased expression of TROP2. A close association exists between the pathological T stage and TROP2 overexpression in pulmonary squamous cell carcinomas [2]. Poorly differentiated lung tumors tend to exhibit increased expression of TROP2. TROP2 also influences and alters IGF-1R signaling in these tumors [3]. Patients with pulmonary adenocarcinomas, especially those in stage II or III that overexpressTROP2, tend to have a better clinical outcome. They also exhibit better survival rates. Thus, TROP2 overexpression is an important independent marker of prognosis in lung carcinomas.A similar relationship is seen in colorectal carcinomas [4]. Decreased overall survival and increased invasiveness is seen in stage IIB colorectal carcinomas that show upregulation of TROP2. Interestingly, there is differential expression of TROP2 and tumor aggressiveness in between right-and left-sided colorectal carcinomas [5]. For instance, left-sided colorectal carcinomas show significantly higher TROP2 expression in contrast to TROP2 expression in right-sided colon carcinomas. Recent data suggest that TROP2 is an independent parameter influencing prognosis in left-sided colon carcinomas. Tumors with accentuated TROP2 expression also demonstrate more lymph node metastases as well as deeper depth of invasion. In patients with left-sided squamous cell carcinoma and low TROP2 expression, the median survival time is 63.1 months in contrast to 45.9 months in those with high TROP2 expression [5][6][7]. TROP2 expression is also an important parameter that influences the risk of developing hepatic metastasis.About 56 % of gastric malignancies, especially the intestinal type, exhibit TROP2 overexpression [8]. Assessment of TROP2 in intestinal type gastric malignancies is highly significant. In these tumors, TROP2 is an independent parameter that influences cancer recurrence. In lymph nodepositive patients, a negative relationship exists between TROP2 overexpression and disease-free survival as well as overall survival. It promotes cancerogenesis by activating the ERK MAPK pathway [9]. Fifty-five percent of pancreatic malignancies exhibit TROP2 overexpression [10]. In pancreatic malignancies that demonstrate accentuated levels of TROP2, a poor clinical outcome is seen typically. A positive relationship exists between lymph node metastasis and TROP2 overexpression. Similarly, a positive relationship exists between tumor grade and TROP2 overexpression. In the end, TROP2 overexpression is associated with decreased progression-free survival as well as decreased overall survival. The above examples clearly illustrate the role of TROP2 in systemic carcinogenesis and the need for further studies in this regard.

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confidence: 62%

“…A similar relationship is seen in colorectal carcinomas [4]. Decreased overall survival and increased invasiveness is seen in stage IIB colorectal carcinomas that show upregulation of TROP2.…”

supporting

confidence: 62%

TROP2 expression and its evolving role in tumor pathogenesis in systemic tumors

Kapoor¹

2012

Tumor Biol.

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“…Of note, Trop-2 expression appears to discriminate populations with stem-like activity [49], which may be important for initiation and perpetuation of cancers [50,51]. A different role of Trop-2 in cancer growth has been recently reported by Lin et al [52] in lung carcinoma, where Trop-2 is epigenetically downregulated and affected by LOH, resulting in cancer progression via activation of IGF-1R signalling.…”

Section: Discussionmentioning

confidence: 99%

Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma

et al. 2012

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BackgroundEndometrial cancer is the most common gynecologic malignancy in developed countries. Trop-2 is a glycoprotein involved in cellular signal transduction and is differentially overexpressed relative to normal tissue in a variety of human adenocarcinomas, including endometrioid endometrial carcinomas (EEC). Trop-2 overexpression has been proposed as a marker for biologically aggressive tumor phenotypes.MethodsTrop-2 protein expression was quantified using tissue microarrays consisting of formalin-fixed paraffin-embedded specimens from 118 patients who underwent surgical staging from 2001–9 by laparotomy for EEC. Clinicopathologic characteristics including age, stage, grade, lymphovascular space invasion, and medical comorbidities were correlated with immunostaining score. Univariate and multivariate analyses were performed for overall survival, disease-free survival, and progression-free survival in relation to clinical parameters and Trop-2 protein expression.ResultsClinical outcome data were available for 103 patients. Strong Trop-2 immunostaining was significantly associated with higher tumor grade (p=0.02) and cervical involvement (p<0.01). Univariate analyses showed a significant association with reduced disease-free survival (DFS) (p=0.01), and a trend towards significance for overall and progression-free survival (p=0.06 and p=0.05, respectively). Multivariate analyses revealed Trop-2 overexpression and advanced FIGO stage to be independent prognostic factors for poor DFS (p=0.04 and p <0.001, respectively).ConclusionsTrop-2 protein overexpression is significantly associated with higher tumor grade and serves as an independent prognostic factor for DFS in endometrioid endometrial cancer.

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“…As a cell surface receptor, it can recognize specific ligands [6] and increase the level of intracellular calcium [7]. Although the biological function of Trop2 is unclear, accumulating evidence has demonstrated that its expression is elevated in various malignant tissues, whereas in human normal tissues relatively low or no Trop2 expression is observed [8–11].…”

Section: Introductionmentioning

confidence: 99%

Trop2 enhances invasion of thyroid cancer by inducing MMP2 through ERK and JNK pathways

et al. 2017

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BackgroundMounting evidence has showed that Tumor-associated calcium signal transducer 2 (Trop2) is upregulated in various kinds of human cancers and plays important roles in tumorigenesis. However, the expression status and functional significance of Trop2 in thyroid cancer are largely unknown.MethodsWe first determined the expression of Trop2 by using RNAseqV2 data sets for thyroid cancer deposited on The Cancer Genome Atlas (TCGA) website. The expression of Trop2 was then confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. Cell invasion and migration were assessed by conducting Transwell and wound healing assays. Furthermore, we explored the underlying mechanisms by using real-time RT-PCR, Western blot, zymography, and luciferase reporter assays.ResultsIn this study, we demonstrated that the expression of Trop2 was significantly elevated in thyroid cancer and that its expression level was correlated with the tumor-node-metastasis (TNM) staging and N classification. Dysregulation of Trop2 altered the invasive capability of thyroid cancer cells. Further mechanistic study revealed that MMP2 expression was upregulated by Trop2. Moreover, we found that the effects of Trop2 were dependent on ERK and JNK pathways. The results from clinical specimens showed that Trop2 expression correlated with MMP2 expression in primary thyroid cancer.ConclusionThe current study suggests that elevated expression of Trop2 may represent an important molecular hallmark that is biologically and clinically relevant to the progression of thyroid cancer.

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TROP2 is epigenetically inactivated and modulates IGF‐1R signalling in lung adenocarcinoma

Cited by 89 publications

References 47 publications

TROP2 expression and its evolving role in tumor pathogenesis in systemic tumors

TROP2 expression and its evolving role in tumor pathogenesis in systemic tumors

Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma

Trop2 enhances invasion of thyroid cancer by inducing MMP2 through ERK and JNK pathways

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