The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β‐Catenin Signaling Pathway

Daulat, Avais M.; Wagner, Marta; Walton, Alexandra; Baudelet, Emilie; Audebert, Stéphane; Camoin, Luc; Borg, Jean-Paul

doi:10.1002/pmic.201800487

Cited by 14 publications

(14 citation statements)

References 45 publications

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“…[36,63]. We recently provided a comprehensive map of the partners of Scribble and Lano and confirmed interactions between these LAPs and previously described binding partners (βPIX/ GIT, PP1, p0071 among others) [33]. Around 199 proteins are common to the Scribble and Lano networks, whereas 191 and 275 proteins including many PDZ domaincontaining proteins are specifically associated with Scribble and Lano, respectively.…”

Section: Large Scale Network Associated To Lap Proteinssupporting

confidence: 79%

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The Scribble family in cancer: twentieth anniversary

et al. 2020

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Among the more than 160 PDZ containing proteins described in humans, the cytoplasmic scaffold Scribble stands out because of its essential role in many steps of cancer development and dissemination. Its fame has somehow blurred the importance of homologous proteins, Erbin and Lano, all belonging to the LRR and PDZ (LAP) protein family first described twenty years ago. In this review, we will retrace the history of LAP family protein research and draw attention to their contribution in cancer by detailing the features of its members at the structural and functional levels, and highlighting their shared-but also different-implication in the tumoral process.

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Section: Large Scale Network Associated To Lap Proteinssupporting

confidence: 79%

“…1) which recognizes class I PDZ domains such as those found in PSD-95. Interestingly, Lano interacts with Erbin indirectly through PSD-95, and with Scribble most probably through a PDZ domain interaction [13,33].…”

Section: Pdz Domainsmentioning

confidence: 99%

The Scribble family in cancer: twentieth anniversary

et al. 2020

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“…However, despite direct interaction between SCRIB and β-catenin, the localization of β-catenin was not affected by SCRIB [23]. Moreover, there is a controversial report that SCRIB is a negative regulator of Wnt/β-catenin signaling in a epithelial cell polarity model [28]. Therefore, further study is needed to explore the general or specific roles of FAM83H and SCRIB in the regulation of Wnt/β-catenin pathway during tumorigenesis.…”

Section: Agingmentioning

confidence: 98%

FAM83H and SCRIB stabilize β-catenin and stimulate progression of gastric carcinoma

Hussein

Ahmed

et al. 2020

Aging

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FAM83H primarily is known for its function in tooth development. Recently, a role for FAM83H in tumorigenesis, conjunction with MYC and β-catenin, has been suggested. Analysis of public data indicates that FAM83H expression is closely associated with SCRIB expression in human gastric cancers. Therefore, this study investigated the roles of FAM83H and SCRIB in 200 human gastric cancers and gastric cancer cells. In human gastric carcinomas, both the individual and combined expression patterns of the nuclear FAM83H and SCRIB were independent indicators of shorter survival of gastric carcinoma patients. In MKN-45 and NCI-N87 gastric cancer cells, the expression of FAM83H and SCRIB were associated with proliferation and invasiveness of cells. FAM83H-mediated in vivo tumor growth was attenuated with knock-down of SCRIB. Moreover, immunoprecipitation indicates that FAM83H, SCRIB, and β-catenin, form a complex, and knock-down of either FAM83H or SCRIB accelerated proteasomal degradation of β-catenin. In conclusion, this study has found that the individual and combined expression patterns of nuclear FAM83H and SCRIB are prognostic indicators of gastric carcinomas and further suggests that FAM83H and SCRIB are involved in the progression of gastric carcinomas by stabilizing β-catenin.

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“…However, there are conflicting reports that SCRIB acts as a tumor suppressor. Conditional knock-out of SCRIB in the epidermis enhanced epidermal carcinogenesis [31] and SCRIB repressed Wnt signaling in HEK293T cells [32]. Therefore, further study is needed to clarify the role of SCRIB in human cancer.…”

Section: Discussionmentioning

confidence: 99%

SCRIB Is Involved in the Progression of Ovarian Carcinomas in Association with the Factors Linked to Epithelial-to-Mesenchymal Transition and Predicts Shorter Survival of Diagnosed Patients

et al. 2021

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SCRIB is a polarity protein important in maintaining cell junctions. However, recent reports have raised the possibility that SCRIB might have a role in human cancers. Thus, this study evaluated the roles of SCRIB in ovarian cancers. In 102 human ovarian carcinomas, nuclear expression of SCRIB predicted shorter survival of ovarian carcinoma patients, especially in the patients who received post-operative chemotherapy. In SKOV3 and SNU119 ovarian cancer cells, overexpression of SCRIB stimulated the proliferation and invasion of cells. Knockout of SCRIB inhibited in vivo tumor growth of SKOV3 cells and overexpression of SCRIB promoted tumor growth. Overexpression of SCRIB stimulated epithelial-to-mesenchymal transition by increasing the expression of N-cadherin, snail, TGF-β1, and smad2/3, and decreasing the expression of E-cadherin; the converse was observed with inhibition of SCRIB. In conclusion, this study presents the nuclear expression of SCRIB as a prognostic marker of ovarian carcinomas and suggests that SCRIB is involved in the progression of ovarian carcinomas by stimulating proliferation and epithelial-to-mesenchymal transition-related invasiveness.

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The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β‐Catenin Signaling Pathway

Cited by 14 publications

References 45 publications

The Scribble family in cancer: twentieth anniversary

The Scribble family in cancer: twentieth anniversary

FAM83H and SCRIB stabilize β-catenin and stimulate progression of gastric carcinoma

SCRIB Is Involved in the Progression of Ovarian Carcinomas in Association with the Factors Linked to Epithelial-to-Mesenchymal Transition and Predicts Shorter Survival of Diagnosed Patients

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