Caveolin-1 in sarcomas: friend or foe?

Sáinz‐Jaspeado, Miguel; Martín-Liberal, Juan; Lagares-Tena, Laura; Mateo-Lozano, Silvia; Muro, Xavier García del; Tirado, Óscar M.

doi:10.18632/oncotarget.255

Cited by 40 publications

(29 citation statements)

References 50 publications

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“…95 By analogy, even the role of Cav-1 in cancer appears to be ambiguous, because Cav-1 may behave as either a tumor suppressor or oncopromoter depending on the type of tumor. [96][97][98][99][100][101] Our data argue for an important role of Cavin-1 as essential partner of Cav-1 in RMS progression, as we clearly observed that loss of either Cavin-1 or Cav-1 was sufficient to impair cell proliferation, migration and anchorage-independent cell growth, a characteristic predictive of cell transformation in vitro and in vivo. Consistent with this, we also found that an incremental expression of Cavin-1 in RD cells, as causally obtained upon Cav-1 overexpression, led to a very aggressive cell behavior, which was characterized by a remarkable anchorage-independent cell growth.…”

Section: Discussionsupporting

confidence: 58%

Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma

Faggi

Chiarelli

Colombi

et al. 2015

Laboratory Investigation

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Rhabdomyosarcoma (RMS) is a childhood soft tissue tumor with broad expression of markers that are typically found in skeletal muscle. Cavin-1 is a recently discovered protein actively cooperating with Caveolin-1 (Cav-1) in the morphogenesis of caveolae and whose role in cancer is drawing increasing attention. Using a combined in silico and in vitro analysis here we show that Cavin-1 is expressed in myogenic RMS tumors as well as in human and primary mouse RMS cultures, exhibiting a broad subcellular localization, ranging from nuclei and cytosol to plasma membrane. In particular, the coexpression and plasma membrane interaction between Cavin-1 and Cav-1 characterized the proliferation of human and mouse RMS cell cultures, while a downregulation of their expression levels was observed during the myogenic differentiation. Knockdown of Cavin-1 or Cav-1 in the human RD and RH30 cells led to impairment of cell proliferation and migration. Moreover, loss of Cavin-1 in RD cells impaired the anchorage-independent cell growth in soft agar. While the loss of Cavin-1 did not affect the Cav-1 protein levels in RMS cells, Cav-1 overexpression and knockdown triggered a rise or depletion of Cavin-1 protein levels in RD cells, respectively, in turn reflecting on increased or decreased cell proliferation, migration and anchorage-independent cell growth. Collectively, these data indicate that the interaction between Cavin-1 and Cav-1 underlies the cell growth and migration in myogenic tumors. Rhabdomyosarcoma (RMS) is a childhood soft tissue sarcoma exhibiting broad expression of skeletal muscle markers, 1-3 such as Pax7, MyoD, Myogenin, desmin and muscle-specific actin. 4,5 Cells of origin in RMS may be different muscular and non-muscular cell precursors, 6-8 such as muscle satellite cells (SCs), 9-11 and myoblasts 9,10,12-14 or adipocytes, 15 which are responsible of two major histological subtypes known as embryonal (ERMS) and alveolar (ARMS). The most common ERMS variant arises in children usually o5 years on distinct body sites, such as head, neck and genitourinary regions, while ARMS typically arises in the muscular limb extremities of adolescents and is characterized by poorer prognosis. 16 The genomic landscape causative of ERMS is characterized by a number of genetic lesions and/or somatic mutations that deliberately sustain the activity of different receptors, such as IGF1R, FGFR4 and Patched, 17-21 and related downstream pathways (i.e., RAS/ERK, PI3K/AKT and Sonic Hedgehog signaling). 11,22 In addition, defects in tumor suppressors (i.e., p53), 23 cell cycle regulatory genes (i.e., N-Myc, Rb1) 21,24 and structural proteins involved in muscular integrity (i.e., dystrophin, alpha-sarcoglycan and dysferlin) have been reported. [25][26][27][28][29][30] Conversely, ARMS is dominated by the presence of specific chromosomal translocations leading to expression of the fused Pax3-Foxo1 and Pax7-Foxo1 factors, that driving in a cell cycle manner the transcription of several genes normally restricted to the embryonal development f...

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Section: Discussionsupporting

confidence: 58%

Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma

Faggi

Chiarelli

Colombi

et al. 2015

Laboratory Investigation

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“…Llombart-Bosch et al observed an expression of CAV1, which is also a direct target of the EWSR1-FLI1, in 96 % of 385 ES samples [43]. However, the expression of CAV1 has been reported in several other sarcomas, including osteosarcomas and rhabdomyosarcomas [44]. Therefore, these markers might be sensitive for ES, but in view of the lack of specificity, their diagnostic use remains controversial.…”

Section: Discussionmentioning

confidence: 99%

The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma

et al. 2014

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Ewing sarcoma (ES) is a high-grade malignant neoplasm primarily affecting children and young adults. The diagnosis of ES is often difficult because of its broad differential diagnosis comprising a diverse group of small round cell tumors (SRCTs). Although the identification of tumor type-specific fusion genes by molecular testing is the gold standard for the diagnosis of ES, such approaches are not always available in a routine pathology practice. Thus, a reliable immunohistochemical marker is required. A recent study using a limited number of tumor samples has shown that NKX2.2, a putative transcriptional target of EWSR1-FLI1, is a useful marker for the diagnosis of ES. In the present study, the immunohistochemical expression of NKX2.2 was evaluated on 46 genetically confirmed ES and 85 non-ES SRCTs, together with comparative assessment of CD99 and other molecular targets of EWSR1-FLI1, including NR0B1, E2F3, and EZH2. NKX2.2 was expressed in 37 (80 %) of the ES samples with a mostly diffuse and strong staining pattern, and 14 (16 %) of the non-ES SRCTs, including olfactory neuroblastomas, extraskeletal myxoid chondrosarcoma, mesenchymal chondrosarcoma, small cell carcinomas, and Merkel cell carcinoma, also expressed this marker. The sensitivity and specificity of the NKX2.2 expression in this cohort were 80 and 84 %, respectively. The specificity when combined with CD99 was 98 %, with exceptional expression of both markers in only two non-ES SRCTs, including one case each of mesenchymal chondrosarcoma and small cell carcinoma. NR0B1, E2F3, and EZH2 were less sensitive for specific markers for ES when applied singly or in any combination. In conclusion, the study reinforces that NKX2.2 is a useful immunohistochemical marker for ES, and that the combination of CD99 and NKX2.2 is a powerful diagnostic tool that can differentiate ES from other SRCTs.

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“…The immunoreactivity of CAV1 in lung carcinoma is histotype-dependent and CAV1 expression is negative in 85% of lung carcinomas [7]. The majority of primary osteosarcoma and alveolar rhabdomyosarcoma tumors showed significantly lower levels of CAV1 than normal tissues, suggesting its role as a tumour suppressor [8]. In addition, CAV1 expression is associated with better overall survival for osteosarcoma patients [8].…”

Section: Introductionmentioning

confidence: 99%

Caveolin-1 is transcribed from a hypermethylated promoter to mediate colonocyte differentiation and apoptosis

Dasgupta

Thakur

et al. 2015

Experimental Cell Research

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Caveolin-1 in sarcomas: friend or foe?

Cited by 40 publications

References 50 publications

Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma

Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma

The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma

Caveolin-1 is transcribed from a hypermethylated promoter to mediate colonocyte differentiation and apoptosis

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