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Article Open Access

BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible in vitro mechanism of cancer‑induced cachexia

  • Authors:
    • Kazuki Higure
    • Yoshihiko Kitajima
    • Naoya Kimura
    • Shota Ikeda
    • Shohei Matsufuji
    • Tomokazu Tanaka
    • Hirokazu Noshiro
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Saga University Faculty of Medicine, Saga, Saga 849‑8501, Japan
    Copyright: © Higure et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 78
    |
    Published online on: May 13, 2026
       https://doi.org/10.3892/ijo.2026.5891
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Abstract

Gastrointestinal cancer (GIC) frequently causes cancer cachexia, the major feature of which is the loss of skeletal muscle mass. The degradation of muscular proteins by cancer‑derived factors in the major pathogenesis of cancer‑induced muscle wasting is a known phenomenon. However, this mechanism has mainly been demonstrated using rodent cancer cells, and it may not always be applicable to human cancer types. Impaired skeletal muscle differentiation and regeneration have attracted attention as alternative inducers of cancer cachexia. The present study revealed that conditioned medium from four human GIC cell lines inhibited C2C12 myoblast differentiation by inducing the expression of the inhibitor of DNA binding (Id) proteins Id1 and Id3, which mediated via bone morphogenetic protein (BMP)‑Smad signaling. The results suggested that BMP‑Smad1/5/8‑Id signaling inhibited the expression of a MRF member, myogenin and its downstream myogenic genes, thus leading to unsuccessful differentiation into myotubes. Furthermore, the present study identified high levels of BMP4 secretion from these four human GIC cell lines and demonstrated that an inhibitor of BMP receptor, dorsomorphin or abrogation of BMP4 by siRNA in the GIC cells restored myogenic differentiation in C2C12 cells. The present study uncovered, for the first time, that BMP4 derived from human GIC cells exogenously inhibited myoblast differentiation by activating the Smad1/5/8‑Id signaling axis. In the future, this in vitro study may help to elucidate the complicated mechanisms underlying cancer‑induced cachexia in humans.
View Figures

Figure 1

Morphological changes in C2C12 cells
cultured with DM and CM from five human GIC cell lines or mouse
colon cancer C26. (A) The experimental schedule. After C2C12 cells
were cultured in GM for 24 h (shown by fine arrow), myogenic
differentiation was induced by DM or CM from cancer cells
(designated as day 0), and the medium was changed every 24 h by day
4 (shown by bold arrow). The morphological changes of C2C12 were
assessed using phase-contrast microscope. (B) Representative images
of C2C12, which was cultured with DM or CM from mouse C26 cells
from day 1 to day 5. (C) Representative images of C2C12 cells with
CM from five human GIC cells on day 5. Scale bars, 200 μm.
DM, differentiation medium; CM, conditioned medium; GM, growth
medium; GIC, gastrointestinal cancer.

Figure 2

Analysis of gene expression
associated with myogenic differentiation in C2C12 cells which
cultured with DM or CM from control 58As9, HT29 and DLD1 cells. (A)
Cell proliferation of C2C12 myoblast cultured with DM or three GIC
CMs for 5 days (n=3). (B) Immunofluorescence staining of MYH in
C2C12 cells with DM or CMs from three GIC cells on day 5.
Representative images are shown (green, MYH; blue, DAPI). Scale
bar, 100 μm. (C) Differentiation and the fusion indices that
were quantitatively estimated in C2C12 cells with DM or CM from
three GIC cells (n=10). (D) Reverse transcription-quantitative PCR
(n=3) and (E) western blot analysis of Pax7, MyoD, myogenin,
myomaker and myomixer in C2C12 cells with DM or three GIC CMs (on
day 0, day 1 and day 3). All experiments were independently
repeated at least three times. Data are presented as mean ± SD.
Statistical significance was determined by comparison with control
(DM) on each day. ns not significant, *P<0.05,
**P<0.01, ***P<0.001. DM,
differentiation medium; CM, conditioned medium.

Figure 3

Analysis of BMP4 secretion from HT29
and DLD1 cells and BMP-Smad-Id signaling in C2C12 cells. (A)
RT-qPCR (n=3) and (B) WB of BMP4 expression in three GIC cells. (C)
ELISA of human BMP4 in the cell culture supernatants from three GIC
cells cultured for 48 h (n=6). (D) WB of the p-Smad1/5/8, Smad1/5/8
and Smad4 expressions in C2C12 cells cultured with DM or CMs from
three GIC cells on day 0, 1 and 3. (E) RT-qPCR (n=3) and (F) WB
analysis of Id1 and Id3 expressions in C2C12 cells with DM or CMs
from three GIC CMs. All experiments were independently repeated at
least three times. Data are presented as mean ± SD, and statistical
significance was determined by comparison with control (58As9 or
DM) on each day. ***P<0.001. WB, western blotting; p,
phosphorylation; RT-qPCR, reverse transcription-quantitative PCR;
DM, differentiation medium; CM, conditioned medium; GIC,
gastrointestinal cancer.

Figure 4

Dorsomorphin ameliorated the
inhibitory effect of HT29 and DLD1 CMs on myogenic differentiation
in C2C12 cells. (A) Immunofluorescence staining of MYH in C2C12
cells cultured with CM from HT29 and DLD1 on day 5 with or without
Dorsomorphin treatment. Representative images were shown (green,
MYH; blue, DAPI). Scale bar, 100 μm. (B) Differentiation and
fusion indices were quantitatively assessed in C2C12 cells with
HT29 and DLD1 CMs with or without Dorsomorphin (n=10). (C) The
protein expression of MyoD, myogenin, myomaker and myomixer in
C2C12 cells with HT29 and DLD1 CMs with or without Dorsomorphin on
day 1. (D) WB analysis of Smad1/5/8 and p-Smad1/5/8 in C2C12 cells
with HT29 and DLD1 CMs with or without Dorsomorphin on day 1. (E)
Reverse transcription-quantitative PCR (n=3) and (F) WB analysis of
Id1 and Id3 in C2C12 cells with HT29 and DLD1 CMs with or without
Dorsomorphin on day 1. For panels (D) Smad1/5/8 and (F) Id3, the
corresponding GAPDH loading controls were derived from the same
membrane processed on the same experimental day; different exposure
times were used for visualization. All experiments were
independently repeated at least three times, and data are presented
as mean ± SD. Statistical significance was determined by
comparisons between the dorsomorphin-treated and -untreated C2C12
cells with HT29 and DLD1 CMs. ***P<0.001. WB, western
blotting; DM, differentiation medium; CM, conditioned medium.

Figure 5

GIC KATOIII and BxPC3 cells inhibited
myoblast differentiation in C2C12 cells via BMP4-Smad-Id signaling
axis. (A) Representative images and (B) quantification of reversed
effect of Dorsomorphin on the inhibited C2C12 differentiation by
KATOIII, BxPC3, 44As3 and C26 CMs. Immunofluorescence staining of
MYH in C2C12 cells on day 5, which were incubated in CMs of six
cancer cells with or without Dorsomorphin. Scale bar, 100
μm. Differentiation and fusion indices are shown (n=10).
Data are presented as mean ± SD. Statistical significance was
determined by comparison between dorsomorphin-treated and
-untreated C2C12 cells with CM from each cell lines (B). (C) mRNA
expression of Id1 and Id3 in C2C12 cells with DM or CM from each of
the cancer cell lines on day 1 (n=3). Statistical significance was
analyzed compared with control DM. BMP4 protein levels in the (D)
cell lysates and (E) the culture medium (n=3) from the indicated
cancer cell lines. All experiments were independently repeated at
least three times. Data are presented as mean ± SD, and statistical
significance was determined by comparison with control (DM or
58As9). ns not significant, ***P<0.001. DM,
differentiation medium; CM, conditioned medium.

Figure 6

Abrogation of BMP4 by siRNA reversed
the inhibitory effect of HT29 CM on myogenic differentiation in
C2C12 cells. (A) The efficiency of BMP4 knockdown in HT29 cells was
evaluated by (A) RT-qPCR (n=3) and (B) WB analysis. (C) BMP4
secretion from HT29 cell was evaluated by ELISA in triplicate. A
total of two independent experiments were performed. (D)
Representative images and (E) quantification of the effects of
siBMP4 transfection to HT29 cells on C2C12 differentiation.
Immunofluorescence staining of MYH in C2C12 cells on day 5, which
was cultured with DM or CMs from siCtl- and siBMP4-transfected HT29
cells. (D) Scale bar, 100 μm. (E) Differentiation and fusion
indices were estimated and plotted on graph (n=10). (F) WB analysis
of MyoD, myogenin, Myomaker and Myomixer in C2C12 cells on day 1
with DM or CMs from siCtl- and siBMP4-transfected HT29 cells. (G)
RT-qPCR of Id1and Id3 in C2C12 cells on day 1 (n=3). (H) WB
analysis of Id1, Id3 and Smad signaling proteins in C2C12 cells on
day 1 with DM or CMs from siCtl- and siBMP4-HT29 cells. These
experiments were independently repeated at least three times, and
data are presented as mean ± SD. Statistical significance was
determined by comparison between siBMP4 and siCtl.
***P<0.001. si, small interfering; WB, western
blotting; RT-qPCR, reverse transcription-quantitative PCR; ctl,
control; DM, differentiation medium; CM, conditioned medium; p,
phosphorylation.

Figure 7

A possible mechanism of inhibitory
effect of human GIC-derived BMP4 on myoblast differentiation
through Smad-Id signaling. During the normal process of myogenic
differentiation, a heterodimer complex MyoD/E-protein is formed
through each HLH domain and activates the transcription of myogenin
gene via binding to E-box DNA element within its promoter.
Subsequently, myogenin protein transactivates the expression of the
downstream genes, and eventually completes the terminal
differentiation to myotube. By contrast, human GIC cells-derived
BMP4 binds to BMP receptors, which in turn phosphorylates
Smad1/5/8. The p-Smad1/5/8 forms a complex with Smad4 and
translocates to the nucleus. The p-Smad1/5/8-Smad4 complex binds to
the Smad responsive DNA element (SRE) in the Id gene promoter to
upregulate mRNA expression. As Id protein contains an HLH domain,
but it lacks a basic DNA binding region, Id prevents MyoD activity
by forming antagonistic dimers with E-protein through each HLH.
GIC, gastrointestinal cancer; p, phosphorylated; HLH,
helix-loop-helix; BMP, bone morphogenetic protein.
View References

1 

Tisdale MJ: Biology of cachexia. J Natl Cancer Inst. 89:1763–1773. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Argilés JM, Busquets S, Stemmler B and Lopez-Soriano FJ: Cancer cachexia: Understanding the molecular basis. Nat Rev Cancer. 14:754–762. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Gannavarapu BS, Lau SKM, Carter K, Cannon NA, Gao A, Ahn C, Meyer JJ, Sher DJ, Jatoi A, Infante R and Iyengar P: Prevalence and survival impact of pretreatment cancer-associated weight loss: A tool for guiding early palliative care. J Oncol Pract. 14:e238–e250. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Gilmore LA, Olaechea S, Gilmore BW, Gannavarapu BS, Alvarez CM, Ahn C, Iyengar P and Infante RE: A preponderance of gastrointestinal cancer patients transition into cachexia syndrome. J Cahexia Sarcopenia Muscle. 13:2920–2931. 2022. View Article : Google Scholar

5 

Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, et al: Definition and classification of cancer cachexia: An international consensus. Lancet Oncol. 12:489–495. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Norton JA, Shamberger R, Stein TP, Milne GWA and Brennan MF: The influence of tumor-bearing on protein metabolism in the rat. J Surg Res. 30:456–462. 1981. View Article : Google Scholar : PubMed/NCBI

7 

Smith KL and Tisdale MJ: Increased protein degradation and decreased protein synthesis in skeletal muscle during cancer cachexia. Br J Cancer. 67:680–685. 1993. View Article : Google Scholar : PubMed/NCBI

8 

Martin A, Gallot YS and Freyssenet D: Molecular mechanisms of cancer cachexia-related loss of skeletal muscle mass: Data analysis from preclinical and clinical studies. J Cachexia Sarcopenia Muscle. 14:1150–1167. 2023. View Article : Google Scholar : PubMed/NCBI

9 

Acharyya S, Ladner KJ, Nelson LL, Damrauer J, Reiser PJ, Swoap S and Guttridge DC: Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest. 114:370–378. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HGW, Hasselgren PO, Frontera WR, Lee J, Glass DJ and Shoelson SE: IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell. 119:285–298. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Paul PK, Gupta SK, Bhatnagar S, Panguluri SK, Darnay BG, Choi Y and Kumar A: Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice. J Cell Biol. 191:1395–1411. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Cao Z, Zhao K, Jose I, Hoogenraad NJ and Osellame LD: Biomarkers for cancer cachexia: A mini review. Int J Mol Sci. 22:45012021. View Article : Google Scholar : PubMed/NCBI

13 

Gallagher IJ, Stephens NA, MacDonald AJ, Skipworth RJE, Husi H, Greig CA, Ross JA, Timmons JA and Fearon KCH: Suppression of skeletal muscle turnover in cancer cachexia: Evidence from the transcriptome in sequential human muscle biopsies. Clin Cancer Res. 18:2817–2827. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Bonneto A, Penna F, Aversa Z, Mercantini P, Baccino FM, Costelli P, Ziparo V, Lucia S, Fanelli FR and Muscaritoli M: Early changes of muscle insulin-like growth factor-1 and myostatin gene expression in gastric cancer patients. Muscle Nerve. 48:387–392. 2013. View Article : Google Scholar

15 

D'orland C, Marzetti E, François S, Lorenzi M, Conti V, Stasio ED, Rosa F, Brunelli S, Doglietto GB, Pacelli F and Bossola M: Gastric cancer does not affect the expression of atrophy-related genes in human skeletal muscle. Muscle Nerve. 49:528–533. 2014. View Article : Google Scholar

16 

Talbert EE and Guttridge DC: Impaired regeneration: A role for the muscle microenvironment in cancer cachexia. Semin Cell Dev Biol. 54:82–91. 2016. View Article : Google Scholar

17 

Talbert EE, Cuitino MC, Landner KJ, Rajasekerea PV, Siebert M, Shakya R, Leone GW, Ostrowski MC, Paleo B, Weisleder N, et al: Modeling human cancer-induced cachexia. Cell Rep. 28:1612–1622.e4. 2019. View Article : Google Scholar : PubMed/NCBI

18 

Arneson PC and Doles JD: Impaired muscle regeneration in cancer-associated cachexia. Trends in Cancer. 5:579–582. 2019. View Article : Google Scholar : PubMed/NCBI

19 

Penna F, Costamagna D, Fanzani A, Bonelli G, Baccino FM and Costelli P: Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition. PLoS One. 5:e136042010. View Article : Google Scholar : PubMed/NCBI

20 

Ramamoorthy S, Donohue M and Buck M: Decreased Jun-D expression in muscle wasting of human cachexia. Am J Physiol Endocrinol Metab. 297:E392–E401. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Hawke TJ and Garry DJ: Myogenic satellite cells: Physiology to molecular biology. J Appl Physiol (1985). 91:534–551. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Hollenberg SM, Cheng PF and Weintraub H: Use of a conditional MyoD transcription factor in studies of MyoD trans-activation and muscle determination. Proc Natl Acad Sci USA. 90:8028–8032. 1993. View Article : Google Scholar : PubMed/NCBI

23 

Berkes CA and Tapscott SJ: MyoD and the transcriptional control of myogenesis. Semin Cell Dev Biol. 16:585–595. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Zhang Q, Vashisht AA, O'Rourke J, Corbel SY, Moran R, Romero A, Miraglia L, Zhang J, Durrant E, Schmedt C, et al: The microprotein Minion controls cell fusion and muscle formation. Nat Commun. 8:156642017. View Article : Google Scholar : PubMed/NCBI

25 

Ganassi M, Badodi S, Quiroga HPO, Zammit PS, Hinits Y and Hughes SM: Myogenin promotes myocyte fusion to balance fibre number and size. Nat Commun. 9:42322018. View Article : Google Scholar : PubMed/NCBI

26 

Dey BK, Gagan J, Yan Z and Dutta A: miR-26a is required for skeletal muscle differentiation and regeneration in mice. Genes Dev. 26:2180–2191. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Agarwal S, Cholok D, Loder S, Li J, Breuler C, Chung MT, Sung HH, Ranganathan K, Habbouche J, Drake J, et al: mTOR inhibition and BMP signaling act synergistically to reduce muscle fibrosis and improve myofiber regeneration. JCI Insight. 1:e898052016. View Article : Google Scholar : PubMed/NCBI

28 

Benezra R, Davis RL, Lockshon D, Turner DL and Weintraud H: The protein Id: A negative regulator of helix-loop-helix DNA binding proteins. Cell. 61:49–59. 1990. View Article : Google Scholar : PubMed/NCBI

29 

Jen Y, Weintraub H and Benezra R: Overexpression of Id protein inhibits the muscle differentiation program: In vivo association of Id with E2A proteins. Genes Dev. 6:1466–1479. 1992. View Article : Google Scholar : PubMed/NCBI

30 

Clever JL, Sakai Y, Wang RA and Schneider DB: Inefficient skeletal muscle repair in inhibitor of differentiation knockout mice suggests a crucial role for BMP signaling during adult muscle regeneration. Am J Cell Physiol. 298:C1087–C1099. 2010. View Article : Google Scholar

31 

Winbanks CE, Chen JL, Qian H, Liu Y, Bernardo B, Beyer C, Watt KI, Thomson RE, Connor T, Turner BJ, et al: The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass. J Cell Biol. 203:345–357. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Hogan BL: Bone morphogenetic proteins: Multifunctional regulators of vertebrate development. Genes Dev. 10:1580–1594. 1996. View Article : Google Scholar : PubMed/NCBI

33 

Walsh DW, Godson C, Brazil DP and Martin F: Extracellular BMP-antagonist regulation in development and disease: Tied up in knots. Trends Cell Biol. 20:244–256. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Koosha E and Eames BF: Two modulators of skeletal development: BMPs and Proteoglycans. J Dev Biol. 10:152022. View Article : Google Scholar : PubMed/NCBI

35 

Miyazono K, Maeda S and Imamura T: BMP receptor signaling: Transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 16:251–263. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Ogata T, Wozney JM, Benezra R and Noda M: Bone morphogenetic protein 2 transiently enhances expression of a gene, Id (inhibitor of differentiation), encoding a helix-loop-helix molecule in osteoblast-like cells. Proc Natl Acad Sci USA. 90:9219–9222. 1993. View Article : Google Scholar : PubMed/NCBI

37 

Hollnagel A, Oehlmann V, Heymer J, Rüther U and Nordheim A: Id genes are direct targets of bone morphogenetic protein induction in embryonic stem cells. J Biol Chem. 274:19838–19845. 1999. View Article : Google Scholar : PubMed/NCBI

38 

Borok MJ, Mademtzoglou D and Relaix F: Bu-M-P-ing iron: How BMP signaling regulates muscle growth and regeneration. J Dev Biol. 8:42020. View Article : Google Scholar : PubMed/NCBI

39 

Korchynskyi O and Dijke PT: Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter. J Biol Chem. 277:4883–4891. 2002. View Article : Google Scholar

40 

Shepherd TG, Thériault BL and Nachtigal MW: Autocrine BMP4 signalling regulates ID3 proto-oncogene expression in human ovarian cancer cells. Gene. 414:95–105. 2008. View Article : Google Scholar : PubMed/NCBI

41 

Matsufuji S, Kitajima Y, Higure K, Kimura N, Maeda S, Yamada K, Ito K, Tanaka T, Kai K and Noshiro H: A HIF-1α inhibitor combined with palmitic acid and L-carnitine treatment can prevent the fat metabolic reprogramming under hypoxia and induce apoptosis in hepatocellular carcinoma cells. Cancer Metab. 11:252023. View Article : Google Scholar

42 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

43 

Reimann J, Brimah K, Schroder R, Wering A, Beauchamp JR and Partridge TA: Pax7 distribution in human skeletal muscle biopsies and myogenic tissue cultures. Cell Tissue Res. 315:233–242. 2004. View Article : Google Scholar

44 

Borisov AB, Debkov EI and Carlson BM: Differentiation of activated satellite cells in denervated muscle following single fusions in situ and in cell culture. Histochem Cell Biol. 124:13–23. 2005. View Article : Google Scholar : PubMed/NCBI

45 

He WA, Berardi E, Cardillo VM, Acharyya S, Aulino P, Thomas-Ahner J, Wang J, Bloomston M, Muscarella P, Nau P, et al: NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia. J Clin Invest. 123:4821–4835. 2013. View Article : Google Scholar : PubMed/NCBI

46 

Kleeff J, Maruyama H, Ishiwata T, Sawhney H, Friess H, Büchler MW and Korc M: Bone morphogenetic protein 2 exerts diverse effects on cell growth in vitro and is expressed in human pancreatic cancer in vivo. Gastroenterology. 116:1202–1216. 1999. View Article : Google Scholar : PubMed/NCBI

47 

Aoki M, Ishigami S, Uenosono Y, Arigami T, Uchikado Y, Kita Y, Kurahara H, Matsumoto M, Ueno S and Natsugoe S: Expression of BMP-7 in human gastric cancer and its clinical significance. B J Cancer. 104:714–718. 2011. View Article : Google Scholar

48 

Guo X, Xiong L, Zou L and Zhao J: Upregulation of bone morphogenetic protein 4 is associated with poor prognosis in patients with hepatocellular carcinoma. Pathol Oncol Res. 18:635–640. 2012. View Article : Google Scholar : PubMed/NCBI

49 

Yokoyama Y, Watanabe T, Tamura Y, Hashizume Y, Miyazono K and Ehata S: Autocrine BMP-4 signaling is a therapeutic target in colorectal cancer. Cancer Res. 77:4026–4038. 2017. View Article : Google Scholar : PubMed/NCBI

50 

Davis H, Raja E, Miyazono K, Thubakihara Y and Moustakas A: Mechanism of action of bone morphogenetic proteins in cancer. Cytokine Growth Factor Rev. 27:81–92. 2016. View Article : Google Scholar

51 

Murre C, McCaw PS and Baltimore D: A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 56:777–783. 1989. View Article : Google Scholar : PubMed/NCBI

52 

Davis RL, Cheng PF, Lassar AB and Weintraub H: The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell. 60:733–746. 1990. View Article : Google Scholar : PubMed/NCBI

53 

Ishibashi J, Perry RL, Asakura A and Rudnicki MA: MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions. J Cell Biol. 171:471–482. 2005. View Article : Google Scholar : PubMed/NCBI

54 

Parker MH, Perry RLS, Fauteux MC, Berkes CA and Rudnicki MA: MyoD synergizes with the E-protein HEB beta to induce myogenic differentiation. Mol Cell Biol. 26:5771–5783. 2006. View Article : Google Scholar : PubMed/NCBI

55 

Faralli H and Dilworth J: Turning on myogenin in muscle: A paradigm for understanding mechanisms of tissue-specific gene expression. Comp Funct Genomics. 2012:8363742012. View Article : Google Scholar : PubMed/NCBI

56 

Berkes CA, Bergstrom DA, Penn BH, Seaver KJ, Knoepfler PS and Tapscott SJ: Pbx marks genes for activation by MyoD indicating a role for a homeodomain protein in establishing myogenic potential. Mol Cell. 14:465–477. 2004. View Article : Google Scholar : PubMed/NCBI

57 

Gerber AN, Klesert TR, Bergstrom DA and Tapscott SJ: Two domains of MyoD mediate transcriptional activation of genes in repressive chromatin: A mechanism for lineage determination in myogenesis. Genes Dev. 11:436–450. 1997. View Article : Google Scholar : PubMed/NCBI

58 

Lopez MA, Si Y, Hu X, Williams V, Qushair F, Carlyle J, Alesce L, Conklin M, Gilbert S, Bamman MM, et al: Smad8 is increased in duchenne muscular dystrophy and suppresses miR-1, miR-133a, and miR-133b. Int J Mol Sci. 23:75152022. View Article : Google Scholar : PubMed/NCBI

59 

Pasero M, Giovarelli M, Bucci G, Gherzi R and Briata P: Bone morphogenetic protein/SMAD signaling orients cell fate decision by impairing KSRP-dependent microRNA maturation. Cell Rep. 2:1159–1168. 2012. View Article : Google Scholar : PubMed/NCBI

60 

Jin W, Peng J and Jiang S: The epigenetic regulation of embryonic myogenesis and adult muscle regeneration by histone methylation modification. Biochem Biophys Rep. 6:209–219. 2016.PubMed/NCBI

61 

Ono Y, Calhabeu F, Morgan JE, Katagiri T, Amthor H and Zammit PS: BMP signalling permits population expansion by preventing premature myogenic differentiation in muscle satellite cells. Cell Death Differ. 18:222–234. 2011. View Article : Google Scholar :

62 

Terada K, Misao S, Katase N, Nishimatsu S and Nohno T: Interaction of Wnt signaling with BMP/Smad signaling during the transition from cell proliferation to myogenic differentiation in mouse myoblast-derived cells. Int J Cell Biol. 2013:6162942013. View Article : Google Scholar : PubMed/NCBI

63 

Abrams KL, Xu J, Nativelle-Serpentini C, Dabirshahsahebi S and Rogers MB: An Evolutionary and molecular analysis of Bmp2 expression. J Biol Chem. 279:15916–15928. 2004. View Article : Google Scholar : PubMed/NCBI

64 

Miyazono K, Kamiya Y and Morikawa M: Bone morphogenetic protein receptors and signal transduction. J Biochem. 147:35–51. 2010. View Article : Google Scholar

65 

Mueller TD and Nickel J: Promiscuity and specificity in BMP receptor activation. FEBS Lett. 586:1846–1859. 2012. View Article : Google Scholar : PubMed/NCBI

66 

Beppu H, Minowa O, Miyazono K and Kawabata M: cDNA cloning and genomic organization of the mouse BMP type II receptor. Biochem Biophys Res Commun. 235:499–504. 1997. View Article : Google Scholar : PubMed/NCBI

67 

Nakane A, Nakagawa H and Nagata H: Advanced high-content phenotypic screening to identify drugs that ameliorate the inhibition of skeletal muscle cell differentiation induced by cancer cachexia serum. Pharmaceuticals (Basel). 18:4452025. View Article : Google Scholar : PubMed/NCBI

68 

Kosacka M, Dyła T, Chaszczewska-Markowska M, Bogunia-Kubik K and Brzecka A: Decreased thrombospondin-1 and bone morphogenetic protein-4 serum levels as potential indices of advanced stage lung cancer. J Clin Med. 10:38592021. View Article : Google Scholar : PubMed/NCBI

69 

Shi YJ and Pan XT: BMP6 and BMP4 expression in patients with cancer-related anemia and its relationship with hepcidin and s-HJV. Gen Mol Res. 15:gmr.150171302015.

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Copy and paste a formatted citation
Spandidos Publications style
Higure K, Kitajima Y, Kimura N, Ikeda S, Matsufuji S, Tanaka T and Noshiro H: BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible <em>in vitro</em> mechanism of cancer‑induced cachexia. Int J Oncol 69: 78, 2026.
APA
Higure, K., Kitajima, Y., Kimura, N., Ikeda, S., Matsufuji, S., Tanaka, T., & Noshiro, H. (2026). BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible <em>in vitro</em> mechanism of cancer‑induced cachexia. International Journal of Oncology, 69, 78. https://doi.org/10.3892/ijo.2026.5891
MLA
Higure, K., Kitajima, Y., Kimura, N., Ikeda, S., Matsufuji, S., Tanaka, T., Noshiro, H."BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible <em>in vitro</em> mechanism of cancer‑induced cachexia". International Journal of Oncology 69.1 (2026): 78.
Chicago
Higure, K., Kitajima, Y., Kimura, N., Ikeda, S., Matsufuji, S., Tanaka, T., Noshiro, H."BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible <em>in vitro</em> mechanism of cancer‑induced cachexia". International Journal of Oncology 69, no. 1 (2026): 78. https://doi.org/10.3892/ijo.2026.5891
Copy and paste a formatted citation
x
Spandidos Publications style
Higure K, Kitajima Y, Kimura N, Ikeda S, Matsufuji S, Tanaka T and Noshiro H: BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible <em>in vitro</em> mechanism of cancer‑induced cachexia. Int J Oncol 69: 78, 2026.
APA
Higure, K., Kitajima, Y., Kimura, N., Ikeda, S., Matsufuji, S., Tanaka, T., & Noshiro, H. (2026). BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible <em>in vitro</em> mechanism of cancer‑induced cachexia. International Journal of Oncology, 69, 78. https://doi.org/10.3892/ijo.2026.5891
MLA
Higure, K., Kitajima, Y., Kimura, N., Ikeda, S., Matsufuji, S., Tanaka, T., Noshiro, H."BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible <em>in vitro</em> mechanism of cancer‑induced cachexia". International Journal of Oncology 69.1 (2026): 78.
Chicago
Higure, K., Kitajima, Y., Kimura, N., Ikeda, S., Matsufuji, S., Tanaka, T., Noshiro, H."BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible <em>in vitro</em> mechanism of cancer‑induced cachexia". International Journal of Oncology 69, no. 1 (2026): 78. https://doi.org/10.3892/ijo.2026.5891
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