PTRF/Cavin-1 is Essential for Multidrug Resistance in Cancer Cells

Yi, Jae Sung; Mun, Dong Gi; Lee, Hyun; Park, Jun Sub; Lee, Jung Woo; Lee, Jae Seon; Kim, Su Jin; Cho, Bong Rae; Lee, Sang Won; Ko, Young Gyu

doi:10.1021/pr300651m

Cited by 44 publications

(45 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, Cavin-1 was reported to decrease the malignant behavior of prostate PC3 cancer cells through different mechanisms, [89][90][91][92][93] although being essential for the tumor-promoting effect of Cav-1 in pancreatic cancer 94 and for multidrug resistance in breast cancer lines. 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.…”

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…Multidrug-resistance cancer cells have unique plasma membrane lipid composition and organization, specifically increased sphingomyelin and rigidity (213, 224). Increased rigidity is associated with increased lipid rafts, which typically facilitate efficient cellular signaling.…”

Section: Additional Mechanisms By Which Nutritional Bioactives Exert mentioning

confidence: 99%

Nutrient-Gene Interaction in Colon Cancer, from the Membrane to Cellular Physiology

et al. 2016

View full text Add to dashboard Cite

The International Agency for Research on Cancer recently released an assessment classifying red and processed meat as “carcinogenic to humans” on the basis of the positive association between increased consumption and risk for colorectal cancer. Diet, however, can also decrease the risk for colorectal cancer and be used as a chemopreventive strategy. Bioactive dietary molecules, such as n-3 polyunsaturated fatty acids, curcumin, and fermentable fiber, have been proposed to exert chemoprotective effects, and their molecular mechanisms have been the focus of research in the dietary/chemoprevention field. Using these bioactives as examples, this review surveys the proposed mechanisms by which they exert their effects, from the nucleus to the cellular membrane. In addition, we discuss emerging technologies involving the culturing of colonic organoids to study the physiological effects of dietary bioactives. Finally, we address future challenges to the field regarding the identification of additional molecular mechanisms and other bioactive dietary molecules that can be utilized in our fight to reduce the incidence of colorectal cancer.

show abstract

“…[131] Cavin1 play also a role in the MDR in breast cancer. [132] Indeed, Cavin1 is necessary for MDR in cancer cells via the fortification of lipid rafts. Since Cavin1 and Cav1 are co-transcriptionally regulated, a loss of Cavin1 will be associated with a loss of Cav1 as well.…”

Section: Caveolae New Partners and Cancermentioning

confidence: 99%