Browsing by Subject "PROSTATE-CANCER"

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  • Mueller-Schwefe, Gerhard; Ahlbeck, Karsten; Aldington, Dominic; Alon, Eli; Coaccioli, Stefano; Coluzzi, Flaminia; Huygen, Frank; Jaksch, Wolfgang; Kalso, Eija; Kocot-Kepska, Magdalena; Kress, Hans-Georg; Mangas, Ana Cristina; Ferri, Cesar Margarit; Morlion, Bart; Nicolaou, Andrew; Perez Hernandez, Concepcion; Pergolizzi, Joseph; Schaefer, Michael; Sichere, Patrick (2014)
  • Southey, Melissa C.; Goldgar, David E.; Winqvist, Robert; Pylkas, Katri; Couch, Fergus; Tischkowitz, Marc; Foulkes, William D.; Dennis, Joe; Michailidou, Kyriaki; van Rensburg, Elizabeth J.; Heikkinen, Tuomas; Nevanlinna, Heli; Hopper, John L.; Doerk, Thilo; Claes, Kathleen B. M.; Reis-Filho, Jorge; Teo, Zhi Ling; Radice, Paolo; Catucci, Irene; Peterlongo, Paolo; Tsimiklis, Helen; Odefrey, Fabrice A.; Dowty, James G.; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B.; Verhoef, Senno; Carpenter, Jane; Clarke, Christine; Scott, Rodney J.; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K.; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Pelttari, Liisa M.; Butzow, Ralf; kConFab Investigators; Australian Ovarian Canc Study Grp (2016)
    Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1x10-5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9x10-8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p=0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
  • Kuisma, Heli; Bramante, Simona; Rajamäki, Kristiina; Sipilä, Lauri J.; Kaasinen, Eevi; Kaukomaa, Jaana; Palin, Kimmo; Mäkinen, Netta; Sjöberg, Jari; Sarvilinna, Nanna; Taipale, Jussi; Kauppi, Liisa; Tumiati, Manuela; Hassinen, Antti; Pitkäniemi, Janne; Jalkanen, Jyrki; Heikkinen, Sanna; Pasanen, Annukka; Heikinheimo, Oskari; Bützow, Ralf; Välimäki, Niko; Aaltonen, Lauri A. (2021)
    Mechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine leiomyomas are common neoplasms that display relatively few chromosomal aberrations. We hypothesized that if mechanical forces contribute to chromosomal damage, signs of this could be seen in uterine leiomyomas from parous women. We examined the karyotypes of 1946 tumors, and found a striking overrepresentation of chromosomal damage associated with parity. We then subjected myometrial cells to physiological forces similar to those encountered during pregnancy, and found this to cause DNA breaks and a DNA repair response. While mechanical forces acting in constrained cellular environments may thus contribute to neoplastic degeneration, and genesis of uterine leiomyoma, further studies are needed to prove possible causality of the observed association. No evidence for progression to malignancy was found. Many factors have been associated with chromosomal damage, including mechanical forces in a constrained cellular environment. Here the authors reveal an association between parity and chromosomal damage by analysing karyotypes of 1946 uterine leiomyomas.
  • Atkinson, Charlotte; Ray, Roberta M.; Li, Wenjin; Lin, Ming-Gang; Gao, Dao Li; Shannon, Jackilen; Stalsberg, Helge; Porter, Peggy L.; Frankenfeld, Cara L.; Wahala, Kristiina; Thomas, David B.; Lampe, Johanna W. (2016)
    Equol (a bacterial metabolite of the soy isoflavone daidzein) is produced by 30% to 50% of humans and may be associated with health outcomes. We hypothesized that plasma equol would be inversely associated with risks of fibrocystic breast conditions (FBC) and breast cancer (BC). Plasma from women in a breast self-examination trial in Shanghai with BC (n = 269) or FBC (n = 443), and age-matched controls (n = 1027) was analyzed for isoflavones. Equol was grouped into categories (= 45 nmol/L) and, among women with daidzein >= 20 nmol/L, the log(10) equol:daidzein ratio was grouped into tertiles. Where available, non-cancerous tissue (NCT) adjacent to the carcinomas from women with BC were classified as non-proliferative or proliferative (n = 130 and 172, respectively). The lesions from women with FBC were similarly classified (n = 99 and 92, respectively). Odds ratios (OR) and 95% confidence intervals (CI) were calculated across equol categories and tertiles of log(10) equol:daidzein ratio. Equol categories were not associated with FBC or BC >.05). For log(10) equol:daidzein, compared to controls there were positive associations in the mid tertile for proliferative FBC (OR 2.06, 95% CI 1.08-3.93), BC with proliferative NCT (OR 2.95, 95% CI 1.37-6.35), and all BC regardless of histology (OR 2.37, 95% CI 1.43-3.95). However, trends in ORs with increasing plasma equol values or equol:daidzein ratios were not observed (P >.05). The results of this study do not provide evidence that equol plays a role in the etiology of these breast conditions. However, further work is needed to confirm or refute this conclusion. (C) 2016 Elsevier Inc. All rights reserved.
  • Mavaddat, Nasim; Michailidou, Kyriaki; Dennis, Joe; Lush, Michael; Fachal, Laura; Lee, Andrew; Tyrer, Jonathan P.; Chen, Ting-Huei; Wang, Qin; Bolla, Manjeet K.; Yang, Xin; Adank, Muriel A.; Ahearn, Thomas; Aittomäki, Kristiina; Allen, Jamie; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Aronson, Kristan J.; Auer, Paul L.; Auvinen, Päivi; Barrdahl, Myrto; Beane Freeman, Laura E.; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Bremer, Michael; Brenner, Hermann; Brentnall, Adam; Brock, Ian W.; Brooks-Wilson, Angela; Brucker, Sara Y.; Brüning, Thomas; Burwinkel, Barbara; Campa, Daniele; Carter, Brian D.; Castelao, Jose E.; Chanock, Stephen J.; Chlebowski, Rowan; Christiansen, Hans; Clarke, Christine L.; Collée, J. Margriet; Cordina-Duverger, Emilie; Cornelissen, Sten; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Daly, Mary B.; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M.; Ekici, Arif B.; Eliassen, A. Heather; Ellberg, Carolina; Engel, Christoph; Eriksson, Mikael; Evans, D. Gareth; Fasching, Peter A.; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Försti, Asta; Fritschi, Lin; Gabrielson, Marike; Gago-Dominguez, Manuela; Gapstur, Susan M.; García-Sáenz, José A.; Gaudet, Mia M.; Georgoulias, Vassilios; Giles, Graham G.; Gilyazova, Irina R.; Glendon, Gord; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Grenaker Alnæs, Grethe I.; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A.; Håkansson, Niclas; Hamann, Ute; Hankinson, Susan E.; Harkness, Elaine F.; Hart, Steven N.; He, Wei; Hein, Alexander; Heyworth, Jane; Hillemanns, Peter; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Howell, Anthony; Huang, Guanmengqian; Humphreys, Keith; Hunter, David J.; Jakimovska, Milena; Jakubowska, Anna; Janni, Wolfgang; John, Esther M.; Johnson, Nichola; Jones, Michael E.; Jukkola-Vuorinen, Arja; Jung, Audrey; Kaaks, Rudolf; Kaczmarek, Katarzyna; Kataja, Vesa; Keeman, Renske; Kerin, Michael J.; Khusnutdinova, Elza; Kiiski, Johanna I.; Knight, Julia A.; Ko, Yon-Dschun; Kosma, Veli-Matti; Koutros, Stella; Kristensen, Vessela N.; Krüger, Ute; Kühl, Tabea; Lambrechts, Diether; Le Marchand, Loic; Lee, Eunjung; Lejbkowicz, Flavio; Lilyquist, Jenna; Lindblom, Annika; Lindström, Sara; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lubiński, Jan; Lux, Michael P.; MacInnis, Robert J.; Maishman, Tom; Makalic, Enes; Maleva Kostovska, Ivana; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Martens, John W.M.; Martinez, Maria Elena; Mavroudis, Dimitrios; McLean, Catriona; Meindl, Alfons; Menon, Usha; Middha, Pooja; Miller, Nicola; Moreno, Fernando; Mulligan, Anna Marie; Mulot, Claire; Muñoz-Garzon, Victor M.; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Newman, William G.; Nielsen, Sune F.; Nordestgaard, Børge G.; Norman, Aaron; Offit, Kenneth; Olson, Janet E.; Olsson, Håkan; Orr, Nick; Pankratz, V. Shane; Park-Simon, Tjoung-Won; Perez, Jose I.A.; Pérez-Barrios, Clara; Peterlongo, Paolo; Peto, Julian; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Polley, Eric C.; Prentice, Ross; Presneau, Nadege; Prokofyeva, Darya; Purrington, Kristen; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rau-Murthy, Rohini; Rennert, Gad; Rennert, Hedy S.; Rhenius, Valerie; Robson, Mark; Romero, Atocha; Ruddy, Kathryn J.; Ruebner, Matthias; Saloustros, Emmanouil; Sandler, Dale P.; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schumacher, Fredrick; Schürmann, Peter; Schwentner, Lukas; Scott, Christopher; Scott, Rodney J.; Seynaeve, Caroline; Shah, Mitul; Sherman, Mark E.; Shrubsole, Martha J.; Shu, Xiao-Ou; Slager, Susan; Smeets, Ann; Sohn, Christof; Soucy, Penny; Southey, Melissa C.; Spinelli, John J.; Stegmaier, Christa; Stone, Jennifer; Swerdlow, Anthony J.; Tamimi, Rulla M.; Tapper, William J.; Taylor, Jack A.; Terry, Mary Beth; Thöne, Kathrin; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Truong, Thérèse; Tzardi, Maria; Ulmer, Hans-Ulrich; Untch, Michael; Vachon, Celine M.; van Veen, Elke M.; Vijai, Joseph; Weinberg, Clarice R.; Wendt, Camilla; Whittemore, Alice S.; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Yang, Xiaohong R.; Yannoukakos, Drakoulis; Zhang, Yan; Zheng, Wei; Ziogas, Argyrios; Dunning, Alison M.; Thompson, Deborah J.; Chenevix-Trench, Georgia; Chang-Claude, Jenny; Schmidt, Marjanka K.; Hall, Per; Milne, Roger L.; Pharoah, Paul D.P.; Antoniou, Antonis C.; Chatterjee, Nilanjan; Kraft, Peter; García-Closas, Montserrat; Simard, Jacques; Easton, Douglas F. (2019)
    Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
  • Geva, Ravit; Lopez, Juanita; Danson, Sarah; Joensuu, Heikki; Peer, Avivit; Harris, Samuel J.; Souza, Fabricio; Pereira, Kaline M. C.; Perets, Ruth (2019)
    Purpose Concomitant treatment with radium-223 and paclitaxel is a potential option for cancer patients with bone metastases; however, myelosuppression risk during coadministration is unknown. This phase Ib study in cancer patients with bone metastases evaluated the safety of radium-223 and paclitaxel. Methods Eligible patients had solid tumor malignancies with >= 2 bone metastases and were candidates for paclitaxel. Treatment included seven paclitaxel cycles (90 mg/m(2) per week intravenously per local standard of care; 3 weeks on/1 week off) plus six radium-223 cycles (55 kBq/kg intravenously; one injection every 4 weeks, starting at paclitaxel cycle 2). The primary end point was percentage of patients with grade 3/4 neutropenia or thrombocytopenia during coadministration of radium-223 and paclitaxel (cycles 2, 3) versus paclitaxel alone (cycle 1). Results Of 22 enrolled patients, 15 were treated (safety population), with 7 completing all six radium-223 cycles. Treated patients had primary cancers of breast (n = 7), prostate (n = 4), bladder (n = 1), non-small cell lung (n = 1), myxofibrosarcoma (n = 1), and neuroendocrine (n = 1). No patients discontinued treatment from toxicity of the combination. In the 13 patients who completed cycle 3, the rates of grade 3 neutropenia in cycles 2 and 3 were 31% and 8%, respectively, versus 23% in cycle 1; there were no cases of grade 4 neutropenia or grade 3/4 thrombocytopenia. Breast cancer subgroup safety results were similar to the overall safety population. Conclusion Radium-223 was tolerated when combined with weekly paclitaxel, with no clinically relevant additive toxicities. This combination should be explored further in patients with bone metastases.
  • Rosell, Frank; Cross, Hannah B.; Johnsen, Christin B.; Sundell, Janne; Zedrosser, Andreas (2019)
    The invasion of a species can cause population reduction or extinction of a similar native species due to replacement competition. There is a potential risk that the native Eurasian beaver (Castor fiber) may eventually be competitively excluded by the invasive North American beaver (C. canadensis) from areas where they overlap in Eurasia. Yet currently available methods of census and population estimates are costly and time-consuming. In a laboratory environment, we investigated the potential of using dogs (Canis lupus familiaris) as a conservation tool to determine whether the Eurasian or the North American beaver is present in a specific beaver colony. We hypothesized that dogs can discriminate between the two beaver species, via the odorant signal of castoreum from males and females, in two floor platform experiments. We show that dogs detect scent differences between the two species, both from dead beaver samples and from scent marks collected in the field. Our results suggest that dogs can be used as an "animal biosensor" to discriminate olfactory signals of beaver species, however more tests are needed. Next step should be to test if dogs discern between beaver species in the field under a range of weather conditions and habitat types and use beaver samples collected from areas where the two species share the same habitat. So far, our results show that dogs can be used as a promising tool in the future to promote conservation of the native beaver species and eradication of the invasive one. We therefore conclude that dogs may be an efficient non-invasive tool to help conservationist to manage invasive species in Europe, and advocate for European wildlife agencies to invest in this new tool.
  • Le Joncour, Vadim; Laakkonen, Pirjo (2018)
    Accounting for 16 million new cases and 9 million deaths annually, cancer leaves a great number of patients helpless. It is a complex disease and still a major challenge for the scientific and medical communities. The efficacy of conventional chemotherapies is often poor and patients suffer from off-target effects. Each neoplasm exhibits molecular signatures - sometimes in a patient specific manner -that may completely differ from the organ of origin, may be expressed in markedly higher amounts and/ or in different location compared to the normal tissue. Although adding layers of complexity in the understanding of cancer biology, this cancer-specific signature provides an opportunity to develop targeting agents for early detection, diagnosis, and therapeutics. Chimeric antibodies, recombinant proteins or synthetic polypeptides have emerged as excellent candidates for specific homing to peripheral and central nervous system cancers. Specifically, peptide ligands benefit from their small size, easy and affordable production, high specificity, and remarkable flexibility regarding their sequence and conjugation possibilities. Coupled to imaging agents, chemotherapies and/or nanocarriers they have shown to increase the on-site delivery, thus allowing better tumor mass contouring in imaging and increased efficacy of the chemotherapies associated with reduced adverse effects. Therefore, some of the peptides alone or in combination have been tested in clinical trials to treat patients. Peptides have been well-tolerated and shown absence of toxicity. This review aims to offer a view on tumor targeting peptides that are either derived from natural peptide ligands or identified using phage display screening. We also include examples of peptides targeting the high-grade malignant tumors of the central nervous system as an example of the complex therapeutic management due to the tumor's location. Peptide vaccines are outside of the scope of this review. (C) 2017 The Authors. Published by Elsevier Ltd.
  • Salakari, Minna; Pylkkänen, Liisa; Sillanmäki, Lauri; Nurminen, Raija; Rautava, Päivi; Koskenvuo, Markku; Suominen, Sakari (2017)
    Objectives: Among breast cancer (BC) survivors, inadequate social support (SS) is associated with a significant increase in cancer-related mortality and reduction in quality of life (QoL). The aim of the study was to explore perceived SS during BC trajectory by comparing BC survivors, women with depression, women with arterial hypertension, and healthy female controls to each other, and to compare perceived balance of receiving and providing SS. Material and methods: The data of ongoing prospective postal survey was linked with national health registries. Respondents with BC (n = 64), depression (n = 471), arterial hypertension (n = 841) and healthy controls (n = 6274) formed the study population. SS was measured by a Sarason's 6-item shortened version of the Social Support Questionnaire (SSQ). The modified Antonucci's (1986) social support convoy model of the network of individuals was used to measure the dominating direction of SS. Results: The main provider of SS for all participants combined was the spouse or partner (94.3%), close relative (12.0%) and friends (5.4%). In all groups, particularly in the BC and arterial hypertension group, spouse or partner was seen as the most important supporter. The group suffering from depression reported significantly less SS in each domain of appraisal (p <0.001). In total, 24.6% of all respondents reported receipt dominance of SS. Conclusion: SS is a well-known determinant of wellbeing. Our study lends support to the spouse's or the partner's central role during the recovery phase of BC. Identification of factors improving the overall QoL of BC survivors is an important public health challenge. (C) 2017 Elsevier Ltd. All rights reserved.
  • Rajecki, Maria; Sarparanta, Mirkka; Hakkarainen, Tanja; Tenhunen, Mikko; Diaconu, Iulia; Kuhmonen, Venla; Kairemo, Kalevi; Kanerva, Anna-Maija; Airaksinen, Anu J.; Hemminki, Akseli (2012)
  • Staquicini, D. I.; D'Angelo, S.; Ferrara, F.; Karjalainen, K.; Sharma, G.; Smith, T. L.; Tarleton, C. A.; Jaalouk, D. E.; Kuniyasu, A.; Baze, W. B.; Chaffee, B. K.; Hanley, P. W.; Barnhart, K. F.; Koivunen, E.; Marchio, S.; Sidman, R. L.; Cortes, J. E.; Kantarjian, H. M.; Arap, W.; Pasqualini, R. (2018)
    Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D (KLAKLAK)2-containing class of agents. BMTP-78 was validated in cells from patients with acute myeloid leukemia and in a panel of human leukemia and lymphoma cell lines, where it induced dose-dependent cytotoxicity in all samples tested. Based on the in vitro efficacy of BMTP-78, we performed formal good laboratory practice toxicology studies in both rodents (mice and rats) and nonhuman primates (cynomolgus and rhesus monkeys). These analyses represent required steps towards an IND application of BMTP-78 for theranostic first-in-human clinical trials.
  • Karki, Tytti; Tojkander, Sari (2021)
    Biophysical cues from the cellular microenvironment are detected by mechanosensitive machineries that translate physical signals into biochemical signaling cascades. At the crossroads of extracellular space and cell interior are located several ion channel families, including TRP family proteins, that are triggered by mechanical stimuli and drive intracellular signaling pathways through spatio-temporally controlled Ca2+-influx. Mechanosensitive Ca2+-channels, therefore, act as critical components in the rapid transmission of physical signals into biologically compatible information to impact crucial processes during development, morphogenesis and regeneration. Given the mechanosensitive nature of many of the TRP family channels, they must also respond to the biophysical changes along the development of several pathophysiological conditions and have also been linked to cancer progression. In this review, we will focus on the TRPV, vanilloid family of TRP proteins, and their connection to cancer progression through their mechanosensitive nature.
  • He, Huiling; Li, Wei; Wu, Dayong; Nagy, Rebecca; Liyanarachchi, Sandya; Akagi, Keiko; Jendrzejewski, Jaroslaw; Jiao, Hong; Hoag, Kevin; Wen, Bernard; Srinivas, Mukund; Waidyaratne, Gavisha; Wang, Rui; Wojcicka, Anna; Lattimer, Ilene R.; Stachlewska, Elzbieta; Czetwertynska, Malgorzata; Dlugosinska, Joanna; Gierlikowski, Wojciech; Ploski, Rafal; Krawczyk, Marek; Jazdzewski, Krystian; Kere, Juha; Symer, David E.; Jin, Victor; Wang, Qianben; de la Chapelle, Albert (2013)
  • Jiu, Yaming; Peränen, Johan; Schaible, Niccole; Cheng, Fang; Eriksson, John E.; Krishnan, Ramaswamy; Lappalainen, Pekka (2017)
    The actin and intermediate filament cytoskeletons contribute to numerous cellular processes, including morphogenesis, cytokinesis and migration. These two cytoskeletal systems associate with each other, but the underlying mechanisms of this interaction are incompletely understood. Here, we show that inactivation of vimentin leads to increased actin stress fiber assembly and contractility, and consequent elevation of myosin light chain phosphorylation and stabilization of tropomyosin-4.2 (see Geeves et al., 2015). The vimentin-knockout phenotypes can be rescued by re-expression of wild-type vimentin, but not by the non-filamentous ` unit length form' vimentin, demonstrating that intact vimentin intermediate filaments are required to facilitate the effects on the actin cytoskeleton. Finally, we provide evidence that the effects of vimentin on stress fibers are mediated by activation of RhoA through its guanine nucleotide exchange factor GEF-H1 (also known as ARHGEF2). Vimentin depletion induces phosphorylation of the microtubule-associated GEF-H1 on Ser886, and thereby promotes RhoA activity and actin stress fiber assembly. Taken together, these data reveal a new mechanism by which intermediate filaments regulate contractile actomyosin bundles, and may explain why elevated vimentin expression levels correlate with increased migration and invasion of cancer cells.