Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation

Nissrine Daou (1, 2) , Medhi Hassani (1, 2, 3) , Emidio Matos (4) , Gabriela Salim de Castro (5) , Raquel Galvao Figueredo Costa (5) , Marilia M. Seelaender (5) , Viviana Moresi (3) , Marco Rocchi (6) , Sergio Adamo (3) , Zhenlin Li (1, 2) , Onnik Agbulut (1, 2) , Dario Coletti (1, 2, 3)

1 IBPS - Institut de Biologie Paris Seine
2 B2A-IBPS - Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing
3 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
4 Federal University of Piauí
5 USP - Universidade de São Paulo = University of São Paulo
6 Università degli Studi di Urbino 'Carlo Bo'

An idiopathic myopathy characterized by central nuclei in muscle fibers, a hallmark of muscle regeneration, has been observed in cancer patients. In cancer cachexia skeletal muscle is incapable of regeneration, consequently, this observation remains unaccounted for. In C26-tumor bearing, cachectic mice, we observed muscle fibers with central nuclei in the absence of molecular markers of bona fide regeneration. These clustered, non-peripheral nuclei were present in NCAM-expressing muscle fibers. Since NCAM expression is upregulated in denervated myofibers, we searched for additional makers of denervation, including AchRs, MUSK, and HDAC. This last one being also consistently upregulated in cachectic muscles, correlated with an increase of central myonuclei. This held true in the musculature of patients suffering from gastrointestinal cancer, where a progressive increase in the number of central myonuclei was observed in weight stable and in cachectic patients, compared to healthy subjects. Based on all of the above, the presence of central myonuclei in cancer patients and animal models of cachexia is consistent with motor neuron loss or NMJ perturbation and could underlie a previously neglected phenomenon of denervation, rather than representing myofiber damage and regeneration in cachexia. Similarly to aging, denervation-dependent myofiber atrophy could contribute to muscle wasting in cancer cachexia.

Mots clés: Central nuclei; altered innervation; c26-colon carcinoma; cancer cachexia; muscle regeneration; striated muscles

Domaines: Cancer; Physiologie [q-bio.TO]

Nissrine Daou, Medhi Hassani, Emidio Matos, Gabriela Salim de Castro, Raquel Galvao Figueredo Costa, et al.. Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation. International Journal of Molecular Sciences, 2020, 21 (3), pp.1092. ⟨10.3390/ijms21031092⟩. ⟨hal-02570056⟩