Engulfment and Cell Motility 1 (ELMO1) Regulates Tumor Cell Behavior and Predicts Prognosis in Colorectal Cancer

Park, Young‐Lan; Cho, Sung-Bum; Park, Sunyoung; Oh, Hyung-Hoon; Myung, Eun; Im, Chan-Muk; Son, Seyeong; Kim, Seung-Hee; Cho, Seo-Yeon; Chung, Min-Woo; Hong, Jeongsoo; Kim, Ki‐Hyun; Myung, Dae‐Seong; Lee, Wan‐Sik; Park, Daeho; Joo, Young‐Eun

doi:10.21873/anticanres.16058

Cited by 6 publications

(3 citation statements)

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“…The PI3K/AKT signal is a representative signaling pathway that induces anti-apoptosis and is known to be activated by Elmo1. Previous studies reported that Elmo1 knockdown inhibited tumor cell proliferation through apoptosis in colorectal cancer SW480 and DLD1 cells, and that induction of apoptosis was associated with downregulation of AKT phosphorylation levels 39 . The cytoprotective effects of Dock180 and Elmo1 have been shown to be mediated by Rac1, p21-activated kinase, and AKT signaling 31 .…”

Section: Discussionmentioning

confidence: 93%

Overexpression of Dock180 and Elmo1 in Melanoma is Associated with Cell Survival and Migration

Lee,

Choi,

Kim

et al. 2023

Ann Dermatol

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Background Melanoma is one of the most aggressive and metastatic skin cancers. Although overexpression of Dock180 and Elmo1 has been identified in various cancers, including glioma, ovarian cancer, and breast cancer, their expression and functions in melanoma remain unknown. Objective This study aims to confirm the expression of Dock180 and Elmo1, their underlying mechanisms, and roles in melanoma. Methods Both immunohistochemical staining and Western blotting were used to confirm expression of Dock180 and Elmo1 in human melanoma. To identify roles of Dock180 and Elmo1 in cell survival, apoptosis and migration, downregulation of Dock180 or Elmo1 in melanoma cells with small interfering RNA (siRNA) was performed. Results We identified overexpression of Dock180 and Elmo1 in human melanoma compared to normal skin ex vivo . Inhibition of Dock180 or Elmo1 following siRNA in melanoma cells reduced cell viability and increased apoptosis as supported by increased proportion of cells with Annexin V-PE (+) staining and sub-G0/G1 peak in cell cycle analysis. Moreover, inhibition of Dock180 or Elmo1 regulated apoptosis-related proteins, showing downregulation of Bcl-2, caspase-3, and PARP and upregulation of Bax, PUMA, cleaved caspase-3, and cleaved PARP. Furthermore, knockdown of Dock180 and Elmo1 in melanoma cells reduced cell migration and changed cellular signaling pathways including ERK and AKT. Vemurafenib decreased cell viability in concentration-dependent manner, while transfection with Dock180- or Elmo1-specific siRNA in melanoma cells significantly reduced cell viability. Conclusion Our results suggest that both Dock180 and Elmo1 may be associated with cancer progression, and can be potential targets for treatment of melanoma.

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Section: Discussionmentioning

confidence: 93%

Overexpression of Dock180 and Elmo1 in Melanoma is Associated with Cell Survival and Migration

Lee,

Choi,

Kim

et al. 2023

Ann Dermatol

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“…This inconsistent function of miR-452-5p may be due to differences in cell lines and their tissue specificity. The expression levels of GSK3β and E-cadherin have been implicated in migration, chemotaxis, metastasis, and clinical prognosis in colorectal cancer cell lines and tissues (23), and further studies on the relationship between these factors are needed.…”

Section: Discussionmentioning

confidence: 99%

Role of Mir-452-5p Overexpression in Epithelial–Mesenchymal Transition (EMT) in Early-stage Colorectal Cancer

KOYAMA,

FUJIHARA,

CHIYO

et al. 2023

In Vivo

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Background/Aim: The microRNA miR-452-5p holds a critical role in the progression of multiple tumor formations, but there is limited understanding regarding the epithelial-mesenchymal transition (EMT) progression and its underlying mechanisms in the early-stage colorectal cancer (CRC). We aimed to explore the change in miRNA expression in early-stage CRC and examine the role of these miRNAs in CRC. Materials and Methods: The expression levels of miR-452-5p in tissues and cells of early-stage CRC were determined by real-time quantitative polymerase chain reaction. Additionally, the biological effects of miR-452-5p on CRC were investigated by in vitro functional experiments. Results: The expression levels of miR-452-5p were found increased in early-stage CRC tissue. We found that miR-452-5p promoted CRC cell proliferation but inhibited epithelialmesenchymal transition. Furthermore, miR-452-5p promoted cell proliferation through activation of the extracellular signal-regulated kinase pathway, and inhibited cell invasion through suppression of Slug (Snail2) expression and upregulation of E-cadherin expression. Conclusion: The expression of miR-452-5p is up-regulated in early CRC and suppresses epithelial-mesenchymal transition in CRC. These discoveries suggest that miR-452-5p has the potential to serve as a viable therapeutic target for CRC.

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“…Engulfment and cell motility protein 1 has been reported to play a vital role in multiple diseases, including inflammatory bowel disease, osteoporosis, and various cancers. [29][30][31][32] Evidence has indicated the positive effects of ELMO1 on promoting cancer cell proliferation, invasion, and metastasis. 16,33,34 In order to understand the relationship between ELMO1 and CRC, we first detected the ELMO1 expression level in CRC tissue.…”

Section: Discussionmentioning

confidence: 99%

Engulfment and cell motility protein 1 fosters reprogramming of tumor‐associated macrophages in colorectal cancer

Wen

Ruan

et al. 2022

Cancer Science

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Functional reprogramming of tumor‐associated macrophages (TAMs) is crucial to their potent tumor‐supportive capacity. However, the molecular mechanism behind the reprogramming process remains poorly understood. Here, we identify engulfment and cell motility protein 1 (ELMO1) as a crucial player for TAM reprogramming in colorectal cancer (CRC). The expression of ELMO1 in stromal but not epithelial tumor cells was positively associated with advanced clinical stage and poor disease‐free survival in CRC. An increase in ELMO1 expression was specifically found in TAMs, but not in other multiple nonmalignant stromal cells. Gain‐ and loss‐of‐function assays indicated ELMO1 reprogrammed macrophages to a TAM‐like phenotype through Rac1 activation. In turn, ELMO1‐reprogrammed macrophages were shown to not only facilitate the malignant behaviors of CRC cells but exhibited potent phagocytosis of tumor cells. Taken together, our work underscores the importance of ELMO1 in determining functional reprogramming of TAMs and could provide new insights on potential therapeutic strategies against CRC.

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Engulfment and Cell Motility 1 (ELMO1) Regulates Tumor Cell Behavior and Predicts Prognosis in Colorectal Cancer

Cited by 6 publications

References 0 publications

Overexpression of Dock180 and Elmo1 in Melanoma is Associated with Cell Survival and Migration

Overexpression of Dock180 and Elmo1 in Melanoma is Associated with Cell Survival and Migration

Role of Mir-452-5p Overexpression in Epithelial–Mesenchymal Transition (EMT) in Early-stage Colorectal Cancer

Engulfment and cell motility protein 1 fosters reprogramming of tumor‐associated macrophages in colorectal cancer

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