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. 2020 May;235(5):4559-4570.
doi: 10.1002/jcp.29332. Epub 2019 Oct 21.

SMARCD1 is a transcriptional target of specific non-hotspot mutant p53 forms

Raju S R Adduri  1   2 , Sara A George  1   3 , Padmavathi Kavadipula  1 , Murali D Bashyam  1   4
Affiliations

SMARCD1 is a transcriptional target of specific non-hotspot mutant p53 forms

Raju S R Adduri et al. J Cell Physiol. 2020 May.

Abstract

Though primarily a tumor suppressor, TP53 harboring specific missense mutations located in the region encoding the DNA binding domain exhibits a gain of function by transcriptional activation of oncogenes. We performed microarray-based messenger RNA profiling of squamous cell carcinoma of the oral tongue (SCCOT) and identified significant elevation of SMARCD1 in samples exhibiting p53 nuclear stabilization. Activation of SMARCD1 by mutant p53 was confirmed by evaluation of additional tongue cancer samples as well as The Cancer Genome Atlas expression datasets. SMARCD1 knockdown in HNSCC cells resulted in a significant reduction in several tumorigenic characteristics including cell viability, ability to form colonies in liquid and solid media and cell migration. We identified significantly increased SMARCD1 transcript levels in tumor versus matched normal samples in SCCOT as well as in other cancer types. Increased SMARCD1 expression predicted poor survival in HNSCC tumors harboring missense p53 mutations. Our results suggest SMARCD1 to be a novel transcriptional target of mutant p53.

Keywords: SMARCD1; ZMAT3; gain of oncogenic function; mutant p53; squamous cell carcinoma of the oral tongue.

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References

REFERENCES

    1. Adduri, R. S., Sr., Kotapalli, V., Gupta, N. A., Gowrishankar, S., Srinivasulu, M., Ali, M. M., … Bashyam, M. D. (2014). P53 nuclear stabilization is associated with FHIT loss and younger age of onset in squamous cell carcinoma of oral tongue. BMC Clinical Pathology, 14, 37. https://doi.org/10.1186/1472-6890-14-37
    1. Adduri, R. S., Katamoni, R., Pandilla, R., Madana, S. N., Paripati, A. K., Kotapalli, V., & Bashyam, M. D. (2014). TP53 Pro72 allele is enriched in oral tongue cancer and frequently mutated in esophageal cancer in India. PLoS One, 9(12), e114002. https://doi.org/10.1371/journal.pone.0114002
    1. Alajem, A., Biran, A., Harikumar, A., Sailaja, B. S., Aaronson, Y., Livyatan, I., … Meshorer, E. (2015). Differential association of chromatin proteins identifies BAF60a/SMARCD1 as a regulator of embryonic stem cell differentiation. Cell Reports, 10(12), 2019-2031. https://doi.org/10.1016/j.celrep.2015.02.064
    1. Barbacid, M. (1990). ras oncogenes: Their role in neoplasia. European Journal of Clinical Investigation, 20(3), 225-235.
    1. Boyle, J. O., Hakim, J., Koch, W., van der Riet, P., Hruban, R. H., Roa, R. A., … Sidransky, D. (1993). The incidence of p53 mutations increases with progression of head and neck cancer. Cancer Research, 53(19), 4477-4480.

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