Tumor-suppressive signaling in the uterus

Li, Qinglei

doi:10.1073/pnas.1821606116

Cited by 7 publications

(2 citation statements)

References 20 publications

(33 reference statements)

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“…The RAS is a complex and vital biochemical pathway that maintains plasma sodium concentration, arterial blood pressure, and extracellular volume. The RAS consists of three main components: angiotensinogen, renin, and angiotensin-converting enzyme (ACE) ( Figure 1 ) ( 11 ). Renin, a hormone secreted by the kidneys, acts on its substrate to catalyze the transformation of angiotensinogen into angiotensin I. Angiotensin I is known to be a powerful vasoconstrictor that contributes to the development of hypertension.…”

Section: The Renin–angiotensin Systemmentioning

confidence: 99%

Unraveling the relationship between the renin–angiotensin system and endometrial cancer: a comprehensive review

Khan,

Elsori,

Rashid

et al. 2023

Front. Oncol.

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Endometrial cancer (EC), the most common adenocarcinoma, represents 90% of uterine cancer in women with an increased incidence of occurrence attributed to age, obesity, hypertension, and hypoestrogenism. Being the most common gynecological malignancy in women, it shows a relation with the activation of different components of the renin–angiotensin system (RAS), which is predominantly involved in maintaining blood pressure, salt, water, and aldosterone secretion, thereby playing a significant role in the etiology of hypertension. The components of the RAS, i.e., ACE-I, ACE-II, AT1R, AT2R, and Pro(renin) receptor, are widely expressed in both glandular and stromal cells of the endometrium, with varying levels throughout the different phases of the menstrual cycle. This causes the endometrial RAS to implicate angiogenesis, neovascularization, and cell proliferation. Thus, dysfunctioning of the endometrial RAS could predispose the growth and spread of EC. Interestingly, the increased expression of AngII, AGTR1, and AGTR2 showed advancement in the stages and progression of EC via the prorenin/ATP6AP2 and AngII/AGTR1 pathway. Therefore, this review corresponds to unraveling the relationship between the progression and development of endometrial cancer with the dysfunction in the expression of various components associated with RAS in maintaining blood pressure.

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Section: The Renin–angiotensin Systemmentioning

confidence: 99%

Unraveling the relationship between the renin–angiotensin system and endometrial cancer: a comprehensive review

Khan,

Elsori,

Rashid

et al. 2023

Front. Oncol.

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“…TGFβ and BMP ligands bind to membrane-bound type II and type I receptors and induce signal transduction via the respective SMAD2/3 and SMAD1/5/8 in concert with a common SMAD, SMAD4. Dysregulation of TGFβ signaling provokes cancer development [2,10,11]. Studies using genetically modified mouse models demonstrate the critical role of TGFβ signaling in sex cord-stromal tumor development [2,12].…”

Section: Introductionmentioning

confidence: 99%

Sertoli Cell-Specific Activation of Transforming Growth Factor Beta Receptor 1 Leads to Testicular Granulosa Cell Tumor Formation

Fang,

Nie,

Putluri

et al. 2023

Cells

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The transforming growth factor β (TGFβ) superfamily, consisting of protein ligands, receptors, and intracellular SMAD transducers, regulates fundamental biological processes and cancer development. Our previous study has shown that sustained activation of TGFβ receptor 1 (TGFBR1) driven by anti-Mullerian hormone receptor type 2 (Amhr2)-Cre in the mouse testis induces the formation of testicular granulosa cell tumors (TGCTs). As Amhr2-Cre is expressed in both Sertoli cells and Leydig cells, it remains unclear whether the activation of TGFBR1 in Sertoli cells alone is sufficient to induce TGCT formation. Therefore, the objective of this study was to determine whether Sertoli cell-activation of TGFBR1 drives oncogenesis in the testis. Our hypothesis was that overactivation of TGFBR1 in Sertoli cells would promote their transdifferentiation into granulosa-like cells and the formation of TGCTs. To test this hypothesis, we generated mice harboring constitutive activation of TGFBR1 in Sertoli cells using anti-Mullerian hormone (Amh)-Cre. Disorganized seminiferous tubules and tumor nodules were found in TGFBR1CA; Amh-Cre mice. A histological analysis showed that Sertoli cell-specific activation of TGFBR1 led to the development of neoplasms resembling granulosa cell tumors, which derailed spermatogenesis. Moreover, TGCTs expressed granulosa cell markers including FOXL2, FOXO1, and INHA. Using a dual fluorescence reporter line, the membrane-targeted tdTomato (mT)/membrane-targeted EGFP (mG) mouse, we provided evidence that Sertoli cells transdifferentiated toward a granulosa cell fate during tumorigenesis. Thus, our findings indicate that Sertoli cell-specific activation of TGFBR1 leads to the formation of TGCTs, supporting a key contribution of Sertoli cell reprogramming to the development of this testicular malignancy in our model.

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Understanding Obesity as a Risk Factor for Uterine Tumors Using Drosophila

Liu

2019

Advances in Experimental Medicine and Biology

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Tumor-suppressive signaling in the uterus

Cited by 7 publications

References 20 publications

Unraveling the relationship between the renin–angiotensin system and endometrial cancer: a comprehensive review

Unraveling the relationship between the renin–angiotensin system and endometrial cancer: a comprehensive review

Sertoli Cell-Specific Activation of Transforming Growth Factor Beta Receptor 1 Leads to Testicular Granulosa Cell Tumor Formation

Understanding Obesity as a Risk Factor for Uterine Tumors Using Drosophila

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