<i>cd44</i> deletion suppresses atypia in the precancerous mouse testis

Li, Huaibiao; Shukla, Shalmali; Frappart, Lucien; Herrlich, Peter; Ploubidou, Aspasia

doi:10.1002/mc.22961

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…Likewise, the ductular proliferation (Figures 2-4) and liver size (Figure 1a) were unaffected by Cd44 loss. In contrast to our study, previous reports demonstrated that deletion of the Cd44 gene inhibits initiation of colon carcinoma in Apc(Min/+) mice [61] and oncogenic progression in the testis of RHAMM-deficient mice [62]. Thus, our results suggest that deletion of Nf2 may specifically release tumorpromoting mechanisms that are independent of CD44; or alternatively, CD44 function is compensated by other molecules in Cd44-deficient Nf2-mutant mice.…”

Section: Icam-1 May Overtake Cd44 Function As a Coreceptor Of Recepto...contrasting

confidence: 99%

Deletion of Cd44 Inhibits Metastasis Formation of Liver Cancer in Nf2-Mutant Mice

Gerardo-Ramírez

Giam

Becker

et al. 2023

Cells

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Primary liver cancer is the third leading cause of cancer-related death worldwide. An increasing body of evidence suggests that the Hippo tumor suppressor pathway plays a critical role in restricting cell proliferation and determining cell fate during physiological and pathological processes in the liver. Merlin (Moesin-Ezrin-Radixin-like protein) encoded by the NF2 (neurofibromatosis type 2) gene is an upstream regulator of the Hippo signaling pathway. Targeting of Merlin to the plasma membrane seems to be crucial for its major tumor-suppressive functions; this is facilitated by interactions with membrane-associated proteins, including CD44 (cluster of differentiation 44). Mutations within the CD44-binding domain of Merlin have been reported in many human cancers. This study evaluated the relative contribution of CD44- and Merlin-dependent processes to the development and progression of liver tumors. To this end, mice with a liver-specific deletion of the Nf2 gene were crossed with Cd44-knockout mice and subjected to extensive histological, biochemical and molecular analyses. In addition, cells were isolated from mutant livers and analyzed by in vitro assays. Deletion of Nf2 in the liver led to substantial liver enlargement and generation of hepatocellular carcinomas (HCCs), intrahepatic cholangiocarcinomas (iCCAs), as well as mixed hepatocellular cholangiocarcinomas. Whilst deletion of Cd44 had no influence on liver size or primary liver tumor development, it significantly inhibited metastasis formation in Nf2-mutant mice. CD44 upregulates expression of integrin β2 and promotes transendothelial migration of liver cancer cells, which may facilitate metastatic spreading. Overall, our results suggest that CD44 may be a promising target for intervening with metastatic spreading of liver cancer.

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Section: Icam-1 May Overtake Cd44 Function As a Coreceptor Of Recepto...contrasting

confidence: 99%

Deletion of Cd44 Inhibits Metastasis Formation of Liver Cancer in Nf2-Mutant Mice

Gerardo-Ramírez

Giam

Becker

et al. 2023

Cells

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“…It has been shown that CD44 is not expressed in normal testes but only in a subset of GCNIS testes and its genetic deletion in the RHAMM truncation background markedly reduces the percentage of mice presenting with germ cell atypia. It is suggested that overexpression of CD44 combined with RHAMM dysfunction drives oncogenesis in the testis [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of CD44 is associated with aggressiveness in seminomas

Labropoulou,

Manou,

Ravazoula

et al. 2024

Mol Biol Rep

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Background Testicular germ cell tumors (TGCTs) exhibit diverse biological and pathological features and are divided in two main types, seminomas and nonseminomatous germ cell tumors (NSGCTs). CD44 is a cell surface receptor, which is highly expressed in malignancies and is implicated in tumorigenesis affecting cell-matrix interactions and cell signaling. Methods and results Here, we examined the expression of CD44 in tumor cell lines and in patients’ material. We found that CD44 is over-expressed in TGCTs compared to normal tissues. Immunohistochemical staining in 71 tissue specimens demonstrated increased expression of CD44 in some patients, whereas CD44 was absent in normal tissue. In seminomas, a high percentage of tumor and stromal cells showed cytoplasmic and/or cell surface staining for CD44 as well as increased staining for CD44 in the tumor stroma was found in some cases. The increased expression of CD44 either in tumor cells or in stromal components was associated with tumor size, nodal metastasis, vascular/lymphatic invasion, and disease stage only in seminomas. The increased stromal expression of CD44 in TGCTs was positively associated with angiogenesis. Conclusions CD44 may exhibit diverse biological functions in seminomas and NSGCTs. The expression of CD44 in tumor cells as well as in tumor stroma fosters an aggressive phenotype in seminomas and should be considered in disease treatment.

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“…[24,[83][84][85][86] Nevertheless, several experimental studies predict that, like CD44, RHAMM can also act as a tumor suppressor in specific contexts. This possibility was first suggested by evidence associating reduced expression or gene dosage of RHAMM with initiation of both seminomas [87] and malignant peripheral nerve sheath tumors, [88] and by experimental evidence that loss of Rhamm exons 10-18 promotes seminoma induction. [89] Furthermore, the progression of pancreatic tumors to metastasis is increased rather than decreased in Rhamm −/− mice [72] that are crossed to transgenic mouse models of pancreatic cancer susceptibility.…”

Section: Rhamm/hmmrmentioning

confidence: 99%

CD44 and RHAMM Are Microenvironmental Sensors with Dual Metastasis Promoter and Suppressor Functions

Tolg,

Hill,

Turley

2024

Advanced Biology

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The progression of primary tumors to metastases remains a significant roadblock to the treatment of most cancers. Emerging evidence has identified genes that specifically affect metastasis and are potential therapeutic targets for managing tumor progression. However, these genes can have dual tumor promoter and suppressor functions that are contextual in manifestation, and that complicate their development as targeted therapies. CD44 and RHAMM/HMMR are examples of multifunctional proteins that can either promote or suppress metastases, as demonstrated in experimental models. These two proteins can be viewed as microenvironmental sensors and this minireview addresses the known mechanistic underpinnings that may determine their metastasis suppressor versus promoter functions. Leveraging this mechanistic knowledge for CD44, RHAMM, and other multifunctional proteins is predicted to improve the precision of therapeutic targeting to achieve more effective management of metastasis.

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cd44 deletion suppresses atypia in the precancerous mouse testis

Cited by 3 publications

References 31 publications

Deletion of Cd44 Inhibits Metastasis Formation of Liver Cancer in Nf2-Mutant Mice

Deletion of Cd44 Inhibits Metastasis Formation of Liver Cancer in Nf2-Mutant Mice

Expression of CD44 is associated with aggressiveness in seminomas

CD44 and RHAMM Are Microenvironmental Sensors with Dual Metastasis Promoter and Suppressor Functions

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