Caveolin‐1 is Markedly Downregulated in Patients with Early‐Stage Colorectal Cancer

Torrejón, Blanca; Cristóbal, Ion; Rojo, Federico; Garcı́a-Foncillas, Jesús

doi:10.1007/s00268-017-4065-9

Cited by 18 publications

(8 citation statements)

References 26 publications

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“…S 3e ). Although its role in metastasis formation is controversially discussed [ 55 ], there is evidence that CAV1 is decreased in early stages of carcinogenesis [ 56 , 57 ], but is found to be elevated at later stages [ 58 ], including in CRC [ 59 ]. Moreover, increased CAV1 expression in T4-stage CRCs was associated with increased invasiveness [ 60 ], and depletion of CAV1 reduced the invasive properties of human CRC cell lines [ 61 ].…”

Section: Resultsmentioning

confidence: 99%

BRAFV600E drives dedifferentiation in small intestinal and colonic organoids and cooperates with mutant p53 and Apc loss in transformation

et al. 2020

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BRAFV600E confers poor prognosis and is associated with a distinct subtype of colorectal cancer (CRC). Little is known, however, about the genetic events driving the initiation and progression of BRAFV600E mutant CRCs. Recent genetic analyses of CRCs indicate that BRAFV600E often coexists with alterations in the WNT- and p53 pathways, but their cooperation remains ill-defined. Therefore, we systematically compared small and large intestinal organoids from mice harboring conditional BraffloxV600E, Trp53LSL-R172H, and/or Apcflox/flox alleles. Using these isogenic models, we observe tissue-specific differences toward sudden BRAFV600E expression, which can be attributed to different ERK-pathway ground states in small and large intestinal crypts. BRAFV600E alone causes transient proliferation and suppresses epithelial organization, followed by organoid disintegration. Moreover, BRAFV600E induces a fetal-like dedifferentiation transcriptional program in colonic organoids, which resembles human BRAFV600E-driven CRC. Co-expression of p53R172H delays organoid disintegration, confers anchorage-independent growth, and induces invasive properties. Interestingly, p53R172H cooperates with BRAFV600E to modulate the abundance of transcripts linked to carcinogenesis, in particular within colonic organoids. Remarkably, WNT-pathway activation by Apc deletion fully protects organoids against BRAFV600E-induced disintegration and confers growth/niche factor independence. Still, Apc-deficient BRAFV600E-mutant organoids remain sensitive toward the MEK inhibitor trametinib, albeit p53R172H confers partial resistance against this clinically relevant compound. In summary, our systematic comparison of the response of small and large intestinal organoids to oncogenic alterations suggests colonic organoids to be better suited to model the human situation. In addition, our work on BRAF-, p53-, and WNT-pathway mutations provides new insights into their cooperation and for the design of targeted therapies.

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Section: Resultsmentioning

confidence: 99%

BRAFV600E drives dedifferentiation in small intestinal and colonic organoids and cooperates with mutant p53 and Apc loss in transformation

et al. 2020

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“…The roles of Cav-1 in cancers are controversial. In some cancers, such as colorectal cancer [17] and ovarian cancer [18], Cav-1 expression is down-regulated, suggesting that Cav-1 can inhibit such cancer development. Interestingly, it is elevated in other malignancies such as endometrial carcinoma [19], hepatic cancer [20], breast cancer [21], prostate cancer [21], and pancreatic cancer [22], in which Cav-1 propels cell growth and migration and results in cancer deterioration.…”

Section: Overview Of Caveolae and Cav-1mentioning

confidence: 99%

Multifaceted Roles of Caveolin-1 in Lung Cancer: A New Investigation Focused on Tumor Occurrence, Development and Therapy

Shi

Lai

et al. 2020

Cancers

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Lung cancer is one of the most common and malignant cancers with extremely high morbidity and mortality in both males and females. Although traditional lung cancer treatments are fast progressing, there are still limitations. Caveolin-1 (Cav-1), a main component of caveolae, participates in multiple cellular events such as immune responses, endocytosis, membrane trafficking, cellular signaling and cancer progression. It has been found tightly associated with lung cancer cell proliferation, migration, apoptosis resistance and drug resistance. In addition to this, multiple bioactive molecules have been confirmed to target Cav-1 to carry on their anti-tumor functions in lung cancers. Cav-1 can also be a predictor for lung cancer patients’ prognosis. In this review, we have summarized the valuable research on Cav-1 and lung cancer in recent years and discussed the multifaceted roles of Cav-1 on lung cancer occurrence, development and therapy, hoping to provide new insights into lung cancer treatment.

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“…The CAV-1 gene is related to cell metastasis and has been confirmed to play a role in numerous tumors. Torrejón et al confirmed that the expression of CAV-1 in patients with colorectal cancer is usually down-regulated, and exerts a tumor suppressor effect in the early stages of the disease (14). Similarly, CAV-1 also exerts a tumor suppressor effect in breast and ovarian cancers (15,16).…”

Section: Discussionmentioning

confidence: 96%

Caveolin-1 regulates the expression of miR-183 and inhibits the invasion and migration of invasive pituitary adenomas by affecting early growth response 1 (EGR1)/Krueppel-like factor 5 (KLF5) interaction

Ma¹,

Zhang²,

Wang³

et al. 2020

Gland Surg

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Background: This study aims to investigate the mechanism through which Caveolin-1 (CAV-1) regulates the expression of micro ribonucleic acid (miR)-183 in invasive pituitary adenoma (IPA) tissues and GH3 cells, and explore the effects of CAV-1 and miR-183 on the invasion and migration ability of GH3 cells.Methods: Western blotting was used to detect the expression level of CAV-1, early growth response 1 (EGR1) and Krueppel-like factor 5 (KLF5). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-183. The mechanisms of interaction between CAV-1, EGR1, and KLF5 were studied by immunoprecipitation experiments. Transwell and cell scratch tests were used to determine the invasion and migration ability of GH3 cells. The dual-luciferase reporter gene experiment was used to detect the effects of EGR1 and KLF5 on miR-183 luciferase activity and verify the targeting relationship between miR-183 and ezrin. Results:The expression of CAV-1 was up-regulated. However, following the knockdown of CAV-1, the invasion and migration ability of GH3 cells was significantly inhibited (P<0.05). The expression of miR-183 was down-regulated, but the expression level of miR-183 was markedly increased following the knockdown of CAV-1 (P<0.05). The knockdown of CAV-1 inhibited the nuclear ectopic of the EGR1 protein in GH3 cells.At the same time, the interaction between EGR1 and KLF5 in GH3 cells was significantly inhibited (P<0.05).The luciferase activity of miR-183 increased significantly after overexpression of KLF5 while overexpression of EGR1 and KLF5 had no significant effect on intracellular luciferase activity. Overexpression of miR-183 markedly inhibited the luciferase activity of wild-type EZR and the expression of the EZR protein in GH3 cells. Furthermore, the overexpression of miR-183 or the inhibition of EZR can reduce the invasion and migration ability of GH3 cells. The simultaneous overexpression or inhibition of miR-183 and EZR expression has no obvious effect on the invasion and migration ability of GH3 cells.Conclusions: CAV-1 up-regulates the expression of miR-183 by inhibiting the nuclear ectopic of EGR1 and the interaction between EGR1 and KLF5 in GH3 cells. Also, miR-183 negatively regulates the expression of EZR and inhibits the invasion and migration of GH3 cells.

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Caveolin‐1 is Markedly Downregulated in Patients with Early‐Stage Colorectal Cancer

Cited by 18 publications

References 26 publications

BRAFV600E drives dedifferentiation in small intestinal and colonic organoids and cooperates with mutant p53 and Apc loss in transformation

BRAFV600E drives dedifferentiation in small intestinal and colonic organoids and cooperates with mutant p53 and Apc loss in transformation

Multifaceted Roles of Caveolin-1 in Lung Cancer: A New Investigation Focused on Tumor Occurrence, Development and Therapy

Caveolin-1 regulates the expression of miR-183 and inhibits the invasion and migration of invasive pituitary adenomas by affecting early growth response 1 (EGR1)/Krueppel-like factor 5 (KLF5) interaction

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