The staff under threat are mainly journalists and photographers
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One in five editorial jobs are to go at the evening regional newspaper, the Manchester Evening News (MEN).
The Guardian Media Group (GMG) is set to axe the 35 posts as part of a company-wide review.
The National Union of Journalists (NUJ) plans to ballot for strike action if the job losses - mainly journalists and photographers - are compulsory.
Union members gave a unanimous vote of no confidence in the GMG board, the editor and the editorial management.
Staff were told of the job losses at lunchtime on Wednesday.
Statements were also read to workers at the GMG's weekly newspapers across Greater Manchester - including the Rochdale Observer and the Salford Advertiser.
NUJ members said, in the motion passed at a meeting afterwards, that they had no confidence in bosses - including editor Paul Horrocks - and had been "betrayed".
GMG regional chief executive Mark Dodson said the MEN faced "one of the most challenging periods in its history" and must change to "thrive in a digital future".
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Readers will be short-changed by this
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He added: "The changes that we propose unfortunately involve a number of job losses.
"We understand that this is a difficult time for our colleagues but we will work closely with the staff and their representatives to make sure that the process is as straightforward as possible".
Jeremy Dear, General Secretary of the NUJ, said it was a "pretty grim day for staff".
"We don't think the company has made an economic case for the job losses, " he said.
Voluntary redundancies
"The cuts will severely damage the quality of the title and will lead to an increase in workload for staff who remain.
"We have concerns that readers will be short-changed by this."
Mr Dear said that staff had until Wednesday to come forward for voluntary redundancy and that all changes would be implemented by 3 March.
Manchester's listings magazine City Life, also owned by the GMG, closed down last December, with the loss of more than 40 jobs.
GMG said it had "struggled" to publish City Life at a profit for the last 15 years.